Innate immunity in the persistent inflammation, immunosuppression, and catabolism syndrome and its implications for therapy

Frontiers in Immunology

Volumn 9, Issue APR, 2018, Pages

  Horiguchi, Hiroyuki ^a,b   Loftus, Tyler J ^a   Hawkins, Russell B ^a   Raymond, Steven L ^a   Stortz, Julie A ^a   Hollen, McKenzie K ^a   Weiss, Brett P ^a   Miller, Elizabeth S ^a   Bihorac, Azra ^a   Larson, Shawn D ^a   Mohr, Alicia M ^a   Brakenridge, Scott C ^a   Tsujimoto, Hironori ^b   Ueno, Hideki ^b   Moore, Frederick A ^a   Moldawer, Lyle L ^a   Efron, Philip A ^a   The Sepsis and Critical Illness Research Center Investigators, ^a  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^b NATIONAL DEFENSE MEDICAL COLLEGE   (Japan)

Author keywords

Chronic critical illness; Inflammation; Innate immunity; Persistent inflammation immunosuppression and catabolism syndrome; Sepsis

Indexed keywords

ANTIGEN;

ADAPTIVE IMMUNITY; AGE; AGING; ANTIGEN PRESENTATION; APOPTOSIS; BLOOD CLOTTING; BONE MARROW; CANCER PATIENT; CATABOLISM; CATABOLISM SYNDROME; CHRONIC DISEASE; COMPLEMENT ACTIVATION; COMPLEMENT SYSTEM; CRITICAL ILLNESS; DISEASE PREDISPOSITION; EXTRACELLULAR TRAP; HIGH RISK PATIENT; HUMAN; IMMUNE RESPONSE; IMMUNOMODULATION; IMMUNOPATHOLOGY; INFLAMMATION; INJURY; INNATE IMMUNITY; INTESTINE FLORA; KINESIOTHERAPY; MALIGNANT NEOPLASM; METABOLIC DISORDER; MICROBIOME; MYELOID-DERIVED SUPPRESSOR CELL; MYELOPOIESIS; NUTRITIONAL SUPPORT; PATHOPHYSIOLOGY; PERSISTENT INFLAMMATION IMMUNOSUPPRESSION AND CATABOLISM SYNDROME; PERSONALIZED MEDICINE; PHAGOCYTOSIS; PHENOTYPE; PYROPTOSIS; QUALITY OF LIFE; REVIEW; SEPSIS; SIGNAL TRANSDUCTION;

EID: 85045012018     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2018.00595     Document Type: Review

References (272)

1. Gentile LF, Cuenca AG, Efron PA, Ang D, Bihorac A, McKinley BA, et al. Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care. J Trauma Acute Care Surg (2012) 72(6):1491-501. doi:10.1097/TA.0b013e318256e000
2. Mira JC, Brakenridge SC, Moldawer LL, Moore FA. Persistent inflammation, immunosuppression and catabolism syndrome. Crit Care Clin (2017) 33(2):245-58. doi:10.1016/j.ccc.2016.12.001
3. Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol (2018) 14(2):121-37. doi:10.1038/nrneph.2017.165
4. Claridge JA, Leukhardt WH, Golob JF, McCoy AM, Malangoni MA. Moving beyond traditional measurement of mortality after injury: evaluation of risks for late death. J Am Coll Surg (2010) 210(5):788-94. doi:10.1016/j.jamcollsurg.2009.12.035
5. Davidson GH, Hamlat CA, Rivara FP, Koepsell TD, Jurkovich GJ, Arbabi S. Long-term survival of adult trauma patients. JAMA (2011) 305(10):1001-7. doi:10.1001/jama.2011.259
6. Eriksson M, Brattstrom O, Larsson E, Oldner A. Causes of excessive late death after trauma compared with a matched control cohort. Br J Surg (2016) 103(10):1282-9. doi:10.1002/bjs.10197
7. Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, et al. The surviving sepsis campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med (2010) 38(2):367-74. doi:10.1097/CCM.0b013e3181cb0cdc
8. Mira JC, Gentile LF, Mathias BJ, Efron PA, Brakenridge SC, Mohr AM, et al. Sepsis pathophysiology, chronic critical illness, and persistent inflammation-immunosuppression and catabolism syndrome. Crit Care Med (2017) 45(2):253-62. doi:10.1097/CCM.0000000000002074
9. Stortz JA, Murphy TJ, Raymond SL, Mira JC, Ungaro R, Dirain ML, et al. Evidence for persistent immune suppression in patients WHO develop chronic critical illness after sepsis. Shock (2017) 49(3):249-58. doi:10.1097/shk.0000000000000981
10. Mathias B, Delmas AL, Ozrazgat-Baslanti T, Vanzant EL, Szpila BE, Mohr AM, et al. Human myeloid-derived suppressor cells are associated with chronic immune suppression after severe sepsis/septic shock. Ann Surg (2017) 265(4):827-34. doi:10.1097/SLA.0000000000001783
11. Uhel F, Azzaoui I, Gregoire M, Pangault C, Dulong J, Tadie JM, et al. Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in patients with sepsis. Am J Respir Crit Care Med (2017) 196(3):315-27. doi:10.1164/rccm.201606-1143OC
12. Nacionales DC, Gentile LF, Vanzant E, Lopez MC, Cuenca A, Cuenca AG, et al. Aged mice are unable to mount an effective myeloid response to sepsis. J Immunol (2014) 192(2):612-22. doi:10.4049/jimmunol.1302109
13. Nacionales DC, Szpila B, Ungaro R, Lopez MC, Zhang J, Gentile LF, et al. A detailed characterization of the dysfunctional immunity and abnormal myelopoiesis induced by severe shock and trauma in the aged. J Immunol (2015) 195(5):2396-407. doi:10.4049/jimmunol.1500984
14. Hotchkiss RS, Moldawer LL, Opal SM, Reinhart K, Turnbull IR, Vincent JL. Sepsis and septic shock. Nat Rev Dis Primers (2016) 2:16045. doi:10.1038/nrdp.2016.45
15. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol (2010) 11(5):373-84. doi:10.1038/ni.1863
16. Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in TLR4 gene. Science (1998) 282(5396):2085-8. doi:10.1126/science.282.5396.2085
17. Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, et al. CD36 ligands promote sterile inflammation through assembly of a toll-like receptor 4 and 6 heterodimer. Nat Immunol (2010) 11(2):155-61. doi:10.1038/ni.1836
18. Sato M, Sano H, Iwaki D, Kudo K, Konishi M, Takahashi H, et al. Direct binding of Toll-like receptor 2 to zymosan, and zymosan-induced NF-kappa B activation and TNF-alpha secretion are down-regulated by lung collectin surfactant protein A. J Immunol (2003) 171(1):417-25. doi:10.4049/jimmunol.171.1.417
19. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, et al. The innate immune response to bacterial flagellin is mediated by toll-like receptor 5. Nature (2001) 410(6832):1099-103. doi:10.1038/35074106
20. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell (2006) 124(4):783-801. doi:10.1016/j.cell.2006.02.015
21. Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity (2011) 34(5):637-50. doi:10.1016/j.immuni.2011.05.006
22. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by toll-like receptor 3. Nature (2001) 413(6857):732-8. doi:10.1038/35099560
23. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, et al. A toll-like receptor recognizes bacterial DNA. Nature (2000) 408(6813):740-5. doi:10.1038/35047123
24. Tartey S, Takeuchi O. Pathogen recognition and toll-like receptor targeted therapeutics in innate immune cells. Int Rev Immunol (2017) 36(2):57-73. doi:10.1080/08830185.2016.1261318
25. Kingeter LM, Lin X. C-type lectin receptor-induced NF-[kgr]B activation in innate immune and inflammatory responses. Cell Mol Immunol (2012) 9(2):105-12. doi:10.1038/cmi.2011.58
26. Yamasaki S, Ishikawa E, Sakuma M, Hara H, Ogata K, Saito T. Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nat Immunol (2008) 9(10):1179-88. doi:10.1038/ni.1651
27. Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, et al. Activation of innate immune antiviral responses by NOD2. Nat Immunol (2009) 10(10):1073-80. doi:10.1038/ni.1782
28. Coulombe F, Fiola S, Akira S, Cormier Y, Gosselin J. Muramyl dipeptide induces NOD2-dependent Ly6C(high) monocyte recruitment to the lungs and protects against influenza virus infection. PLoS One (2012) 7(5):e36734. doi:10.1371/journal.pone.0036734
29. Skeldon A, Saleh M. The inflammasomes: molecular effectors of host resistance against bacterial, viral, parasitic, and fungal infections. Front Microbiol (2011) 2:15. doi:10.3389/fmicb.2011.00015
30. Loo YM, Fornek J, Crochet N, Bajwa G, Perwitasari O, Martinez-Sobrido L, et al. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol (2008) 82(1):335-45. doi:10.1128/jvi.01080-07
31. Bruns AM, Pollpeter D, Hadizadeh N, Myong S, Marko JF, Horvath CM. ATP hydrolysis enhances RNA recognition and antiviral signal transduction by the innate immune sensor, laboratory of genetics and physiology 2 (LGP2). J Biol Chem (2013) 288(2):938-46. doi:10.1074/jbc.M112.424416
32. Bruns AM, Leser GP, Lamb RA, Horvath CM. The innate immune sensor LGP2 activates antiviral signaling by regulating MDA5-RNA interaction and filament assembly. Mol Cell (2014) 55(5):771-81. doi:10.1016/j.molcel.2014.07.003
33. Byun K, Yoo Y, Son M, Lee J, Jeong GB, Park YM, et al. Advanced glycation end-products produced systemically and by macrophages: a common contributor to inflammation and degenerative diseases. Pharmacol (2017) 177:44-55. doi:10.1016/j.pharmthera.2017.02.030
34. Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ. HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol (2010) 28:367-88. doi:10.1146/annurev.immunol.021908.132603
35. Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, et al. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell (1999) 97(7):889-901. doi:10.1016/S0092-8674(00)80801-6
36. Peng J, Yuan Q, Lin B, Panneerselvam P, Wang X, Luan XL, et al. SARM inhibits both TRIF-and MyD88-mediated AP-1 activation. Eur J Immunol (2010) 40(6):1738-47. doi:10.1002/eji.200940034
37. Kawai T, Akira S. TLR signaling. Cell Death Differ (2006) 13(5):816-25. doi:10.1038/sj.cdd.4401850
38. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell (2010) 140(6):805-20. doi:10.1016/j.cell.2010.01.022
39. Rivera A, Siracusa MC, Yap GS, Gause WC. Innate cell communication kick-starts pathogen-specific immunity. Nat Immunol (2016) 17(4):356-63. doi:10.1038/ni.3375
40. Kazzaz NM, Sule G, Knight JS. Intercellular interactions as regulators of NETosis. Front Immunol (2016) 7:453. doi:10.3389/fimmu.2016.00453
41. Efron P, Moldawer LL. Sepsis and the dendritic cell. Shock (2003) 20(5):386-401. doi:10.1097/01.SHK.0000092698.10326.6f
42. Mantegazza AR, Magalhaes JG, Amigorena S, Marks MS. Presentation of phagocytosed antigens by MHC class I and II. Traffic (2013) 14(2):135-52. doi:10.1111/tra.12026
43. Smyth MJ, Cretney E, Kelly JM, Westwood JA, Street SE, Yagita H, et al. Activation of NK cell cytotoxicity. Mol Immunol (2005) 42(4):501-10. doi:10.1016/j.molimm.2004.07.034
44. Delano MJ, Ward PA. The immune system's role in sepsis progression, resolution, and long-term outcome. Immunol Rev (2016) 274(1):330-53. doi:10.1111/imr.12499
45. Eberl G, Colonna M, Di Santo JP, McKenzie AN. Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology. Science (2015) 348(6237):aaa6566. doi:10.1126/science.aaa6566
46. Opal SM. Phylogenetic and functional relationships between coagulation and the innate immune response. Crit Care Med (2000) 28(9 Suppl):S77-80. doi:10.1097/00003246-200009001-00017
47. Levi M, van der Poll T. Inflammation and coagulation. Crit Care Med (2010) 38(2 Suppl):S26-34. doi:10.1097/CCM.0b013e3181c98d21
48. Osterud B, Bjorklid E. Sources of tissue factor. Semin Thromb Hemost (2006) 32(1):11-23. doi:10.1055/s-2006-933336
49. Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD Jr, et al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A (2010) 107(36):15880-5. doi:10.1073/pnas.1005743107
50. Yeaman MR. Platelets: at the nexus of antimicrobial defence. Nat Rev Microbiol (2014) 12(6):426-37. doi:10.1038/nrmicro3269
51. Ali RA, Wuescher LM, Dona KR, Worth RG. Platelets mediate host defense against Staphylococcus aureus through direct bactericidal activity and by enhancing macrophage activities. J Immunol (2017) 198(1):344-51. doi:10.4049/jimmunol.1601178
52. Gaertner F, Ahmad Z, Rosenberger G, Fan S, Nicolai L, Busch B, et al. Migrating platelets are mechano-scavengers that collect and bundle bacteria. Cell (2017) 171(6):1368.e-82.e. doi:10.1016/j.cell.2017.11.001
53. Foley JH. Examining coagulation-complement crosstalk: complement activation and thrombosis. Thromb Res (2016) 141(Suppl 2):S50-4. doi:10.1016/s0049-3848(16)30365-6
54. Stark RJ, Aghakasiri N, Rumbaut RE. Platelet-derived toll-like receptor 4 (TLR-4) is sufficient to promote microvascular thrombosis in endotoxemia. PLoS One (2012) 7(7):e41254. doi:10.1371/journal.pone.0041254
55. Semeraro F, Ammollo CT, Morrissey JH, Dale GL, Friese P, Esmon NL, et al. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4. Blood (2011) 118(7):1952-61. doi:10.1182/blood-2011-03-343061
56. Ghebrehiwet B. The complement system: an evolution in progress [version 1; referees: 2 approved]. F1000Res (2016) 5:2840. doi:10.12688/f1000research.10065.1
57. Dunkelberger JR, Song WC. Complement and its role in innate and adaptive immune responses. Cell Res (2010) 20(1):34-50. doi:10.1038/cr.2009.139
58. Degn SE, Thiel S. Humoral pattern recognition and the complement system. Scand J Immunol (2013) 78(2):181-93. doi:10.1111/sji.12070
59. Riedemann NC, Guo RF, Sarma VJ, Laudes IJ, Huber-Lang M, Warner RL, et al. Expression and function of the C5a receptor in rat alveolar epithelial cells. J Immunol (2002) 168(4):1919-25. doi:10.4049/jimmunol.168.4.1919
60. Guo RF, Riedemann NC, Laudes IJ, Sarma VJ, Kunkel RG, Dilley KA, et al. Altered neutrophil trafficking during sepsis. J Immunol (2002) 169(1):307-14. doi:10.4049/jimmunol.169.1.307
61. Laudes IJ, Chu JC, Sikranth S, Huber-Lang M, Guo RF, Riedemann N, et al. Anti-c5a ameliorates coagulation/fibrinolytic protein changes in a rat model of sepsis. Am J Pathol (2002) 160(5):1867-75. doi:10.1016/s0002-9440(10)61133-9
62. Lajoie S, Lewkowich IP, Suzuki Y, Clark JR, Sproles AA, Dienger K, et al. Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. Nat Immunol (2010) 11(10):928-35. doi:10.1038/ni.1926
63. Strainic MG, Shevach EM, An F, Lin F, Medof ME. Absence of signaling into CD4(+) cells via C3aR and C5aR enables autoinductive TGF-beta1 signaling and induction of Foxp3(+) regulatory T cells. Nat Immunol (2013) 14(2):162-71. doi:10.1038/ni.2499
64. Vieyra M, Leisman S, Raedler H, Kwan WH, Yang M, Strainic MG, et al. Complement regulates CD4 T-cell help to CD8 T cells required for murine allograft rejection. Am J Pathol (2011) 179(2):766-74. doi:10.1016/j.ajpath.2011.04.038
65. Taylor RP, Ferguson PJ, Martin EN, Cooke J, Greene KL, Grinspun K, et al. Immune complexes bound to the primate erythrocyte complement receptor (CR1) via anti-CR1 mAbs are cleared simultaneously with loss of CR1 in a concerted reaction in a rhesus monkey model. Clin Immunol Immunopathol (1997) 82(1):49-59. doi:10.1006/clin.1996.4286
66. Molina H, Holers VM, Li B, Fung Y, Mariathasan S, Goellner J, et al. Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2. Proc Natl Acad Sci U S A (1996) 93(8):3357-61. doi:10.1073/pnas.93.8.3357
67. Vogt L, Schmitz N, Kurrer MO, Bauer M, Hinton HI, Behnke S, et al. VSIG4, a B7 family-related protein, is a negative regulator of T cell activation. J Clin Invest (2006) 116(10):2817-26. doi:10.1172/jci25673
68. Jane-wit D, Surovtseva YV, Qin L, Li G, Liu R, Clark P, et al. Complement membrane attack complexes activate noncanonical NF-kappaB by forming an Akt+ NIK+ signalosome on Rab5+ endosomes. Proc Natl Acad Sci U S A (2015) 112(31):9686-91. doi:10.1073/pnas.1503535112
69. Sadik CD, Kim ND, Luster AD. Neutrophils cascading their way to inflammation. Trends Immunol (2011) 32(10):452-60. doi:10.1016/j.it.2011.06.008
70. Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol (2011) 11(11):762-74. doi:10.1038/nri3070
71. Suratt BT, Petty JM, Young SK, Malcolm KC, Lieber JG, Nick JA, et al. Role of the CXCR4/SDF-1 chemokine axis in circulating neutrophil homeostasis. Blood (2004) 104(2):565-71. doi:10.1182/blood-2003-10-3638
72. Eash KJ, Greenbaum AM, Gopalan PK, Link DC. CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J Clin Invest (2010) 120(7):2423-31. doi:10.1172/jci41649
73. Delano MJ, Kelly-Scumpia KM, Thayer TC, Winfield RD, Scumpia PO, Cuenca AG, et al. Neutrophil mobilization from the bone marrow during polymicrobial sepsis is dependent on CXCL12 signaling. J Immunol (2011) 187(2):911-8. doi:10.4049/jimmunol.1100588
74. Namikawa R, Muench MO, Roncarolo MG. Regulatory roles of the ligand for Flk2/Flt3 tyrosine kinase receptor on human hematopoiesis. Stem cells (1996) 14(4):388-95. doi:10.1002/stem.140388
75. Scumpia PO, Kelly-Scumpia KM, Delano MJ, Weinstein JS, Cuenca AG, Al-Quran S, et al. Cutting edge: bacterial infection induces hematopoietic stem and progenitor cell expansion in the absence of TLR signaling. J Immunol (2010) 184(5):2247-51. doi:10.4049/jimmunol.0903652
76. Claessens YE, Fontenay M, Pene F, Chiche JD, Guesnu M, Hababou C, et al. Erythropoiesis abnormalities contribute to early-onset anemia in patients with septic shock. Am J Respir Crit Care Med (2006) 174(1):51-7. doi:10.1164/rccm.200504-561OC
77. Ueda Y, Kondo M, Kelsoe G. Inflammation and the reciprocal production of granulocytes and lymphocytes in bone marrow. J Exp Med (2005) 201(11):1771-80. doi:10.1084/jem.20041419
78. Chandra R, Villanueva E, Feketova E, Machiedo GW, Hasko G, Deitch EA, et al. Endotoxemia down-regulates bone marrow lymphopoiesis but stimulates myelopoiesis: the effect of G6PD deficiency. J Leukoc Biol (2008) 83(6):1541-50. doi:10.1189/jlb.1207838
79. Delano MJ, Scumpia PO, Weinstein JS, Coco D, Nagaraj S, Kelly-Scumpia KM, et al. MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis. J Exp Med (2007) 204(6):1463-74. doi:10.1084/jem.20062602
80. Hotchkiss RS, Tinsley KW, Swanson PE, Schmieg RE Jr, Hui JJ, Chang KC, et al. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol (2001) 166(11):6952-63. doi:10.4049/jimmunol.166.11.6952
81. Alamo IG, Kannan KB, Bible LE, Loftus TJ, Ramos H, Efron PA, et al. Daily propranolol administration reduces persistent injury-associated anemia after severe trauma and chronic stress. J Trauma Acute Care Surg (2017) 82(4):714-21. doi:10.1097/ta.0000000000001374
82. Shorr AF, Jackson WL. Transfusion practice and nosocomial infection: assessing the evidence. Curr Opin Crit Care (2005) 11(5):468-72. doi:10.1097/01.ccx.0000176689.18433.f4
83. Youssef LA, Spitalnik SL. Transfusion-related immunomodulation: a reappraisal. Curr Opin Hematol (2017) 24(6):551-7. doi:10.1097/moh.0000000000000376
84. Youn JI, Nagaraj S, Collazo M, Gabrilovich DI. Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol (2008) 181(8):5791-802. doi:10.4049/jimmunol.181.8.5791
85. Dietlin TA, Hofman FM, Lund BT, Gilmore W, Stohlman SA, van der Veen RC. Mycobacteria-induced Gr-1+ subsets from distinct myeloid lineages have opposite effects on T cell expansion. J Leukoc Biol (2007) 81(5):1205-12. doi:10.1189/jlb.1006640
86. Gabrilovich DI, Velders MP, Sotomayor EM, Kast WM. Mechanism of immune dysfunction in cancer mediated by immature Gr-1+ myeloid cells. J Immunol (2001) 166(9):5398-406. doi:10.4049/jimmunol.166.9.5398
87. Cuenca AG, Delano MJ, Kelly-Scumpia KM, Moreno C, Scumpia PO, Laface DM, et al. A paradoxical role for myeloid-derived suppressor cells in sepsis and trauma. Mol Med (2011) 17(3-4):281-92. doi:10.2119/molmed.2010.00178
88. Hatziioannou A, Alissafi T, Verginis P. Myeloid-derived suppressor cells and T regulatory cells in tumors: unraveling the dark side of the force. J Leukoc Biol (2017) 102(2):407-21. doi:10.1189/jlb.5VMR1116-493R
89. Kamran N, Kadiyala P, Saxena M, Candolfi M, Li Y, Moreno-Ayala MA, et al. Immunosuppressive myeloid cells' blockade in the glioma microenvironment enhances the efficacy of immune-stimulatory gene therapy. Mol Ther (2017) 25(1):232-48. doi:10.1016/j.ymthe.2016.10.003
90. Chesney JA, Mitchell RA, Yaddanapudi K. Myeloid-derived suppressor cells-a new therapeutic target to overcome resistance to cancer immunotherapy. J Leukoc Biol (2017) 102(3):727-40. doi:10.1189/jlb.5VMR1116-458RRR
91. Noman MZ, Desantis G, Janji B, Hasmim M, Karray S, Dessen P, et al. PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med (2014) 211(5):781-90. doi:10.1084/jem.20131916
92. Liu CY, Wang YM, Wang CL, Feng PH, Ko HW, Liu YH, et al. Population alterations of L-arginase-and inducible nitric oxide synthase-expressed CD11b+/CD14(-)/CD15+/CD33+ myeloid-derived suppressor cells and CD8+ T lymphocytes in patients with advanced-stage non-small cell lung cancer. J Cancer Res Clin Oncol (2010) 136(1):35-45. doi:10.1007/s00432-009-0634-0
93. Otsuki N, Kamimura Y, Hashiguchi M, Azuma M. Expression and function of the B and T lymphocyte attenuator (BTLA/CD272) on human T cells. Biochem Biophys Res Commun (2006) 344(4):1121-7. doi:10.1016/j.bbrc.2006.03.242
94. Heine A, Held SAE, Schulte-Schrepping J, Wolff JFA, Klee K, Ulas T, et al. Generation and functional characterization of MDSC-like cells. Oncoimmunology (2017) 6(4):e1295203. doi:10.1080/2162402x.2017.1295203
95. Cuenca AG, Cuenca AL, Winfield RD, Joiner DN, Gentile L, Delano MJ, et al. Novel role for tumor-induced expansion of myeloid-derived cells in cancer cachexia. J Immunol (2014) 192(12):6111-9. doi:10.4049/jimmunol.1302895
96. Lim JJ, Grinstein S, Roth Z. Diversity and versatility of phagocytosis: roles in innate immunity, tissue remodeling, and homeostasis. Front Cell Infect Microbiol (2017) 7:191. doi:10.3389/fcimb.2017.00191
97. Green DR, Oguin TH, Martinez J. The clearance of dying cells: table for two. Cell Death Differ (2016) 23(6):915-26. doi:10.1038/cdd.2015.172
98. Mallat M, Marin-Teva JL, Cheret C. Phagocytosis in the developing CNS: more than clearing the corpses. Curr Opin Neurobiol (2005) 15(1):101-7. doi:10.1016/j.conb.2005.01.006
99. Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity (2016) 44(3):450-62. doi:10.1016/j.immuni.2016.02.015
100. Rabinovitch M. Professional and non-professional phagocytes: an introduction. Trends Cell Biol (1995) 5(3):85-7. doi:10.1016/S0962-8924(00)88955-2
101. Nishimura K, Shindo S, Movila A, Kayal R, Abdullah A, Savitri IJ, et al. TRAP-positive osteoclast precursors mediate ROS/NO-dependent bactericidal activity via TLR4. Free Radic Biol Med (2016) 97:330-41. doi:10.1016/j.freeradbiomed.2016.06.021
102. Watanabe K, Misu T, Ohde S, Edamatsu H. Characteristics of eosinophils migrating around fungal hyphae in nasal discharge. Ann Otol Rhinol Laryngol (2004) 113(3 Pt 1):200-4. doi:10.1177/000348940411300305
103. Sprangers S, Behrendt N, Engelholm L, Cao Y, Everts V. Phagocytosis of collagen fibrils by fibroblasts in vivo is independent of the uPARAP/Endo180 receptor. J Cell Biochem (2017) 118(6):1590-5. doi:10.1002/jcb.25821
104. Tian B, Al-Moujahed A, Bouzika P, Hu Y, Notomi S, Tsoka P, et al. Atorvastatin promotes phagocytosis and attenuates pro-inflammatory response in human retinal pigment epithelial cells. Sci Rep (2017) 7(1):2329. doi:10.1038/s41598-017-02407-7
105. Flannagan RS, Harrison RE, Yip CM, Jaqaman K, Grinstein S. Dynamic macrophage "probing" is required for the efficient capture of phagocytic targets. J Cell Biol (2010) 191(6):1205-18. doi:10.1083/jcb.201007056
106. Suvorova ES, Gripentrog JM, Miettinen HM. Different endocytosis pathways of the C5a receptor and the N-formyl peptide receptor. Traffic (2005) 6(2):100-15. doi:10.1111/j.1600-0854.2004.00256.x
107. Rosales C, Uribe-Querol E. Phagocytosis: a fundamental process in immunity. Biomed Res Int (2017) 2017:9042851. doi:10.1155/2017/9042851
108. Pauwels AM, Trost M, Beyaert R, Hoffmann E. Patterns, receptors, and signals: regulation of phagosome maturation. Trends Immunol (2017) 38(6):407-22. doi:10.1016/j.it.2017.03.006
109. Chow A, Toomre D, Garrett W, Mellman I. Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane. Nature (2002) 418(6901):988-94. doi:10.1038/nature01006
110. Joffre OP, Segura E, Savina A, Amigorena S. Cross-presentation by dendritic cells. Nat Rev Immunol (2012) 12(8):557-69. doi:10.1038/nri3254
111. Garrett WS, Chen LM, Kroschewski R, Ebersold M, Turley S, Trombetta S, et al. Developmental control of endocytosis in dendritic cells by Cdc42. Cell (2000) 102(3):325-34. doi:10.1016/S0092-8674(00)00038-6
112. Guermonprez P, Valladeau J, Zitvogel L, Thery C, Amigorena S. Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol (2002) 20:621-67. doi:10.1146/annurev.immunol.20.100301.064828
113. Scumpia PO, McAuliffe PF, O'Malley KA, Ungaro R, Uchida T, Matsumoto T, et al. CD11c+ dendritic cells are required for survival in murine polymicrobial sepsis. J Immunol (2005) 175(5):3282-6. doi:10.4049/jimmunol.175.5.3282
114. Efron PA, Martins A, Minnich D, Tinsley K, Ungaro R, Bahjat FR, et al. Characterization of the systemic loss of dendritic cells in murine lymph nodes during polymicrobial sepsis. J Immunol (2004) 173(5):3035-43. doi:10.4049/jimmunol.173.5.3035
115. Fattahi F, Ward PA. Understanding immunosuppression after sepsis. Immunity (2017) 47(1):3-5. doi:10.1016/j.immuni.2017.07.007
116. Yan J, Li S, Li S. The role of the liver in sepsis. Int Rev Immunol (2014) 33(6):498-510. doi:10.3109/08830185.2014.889129
117. Bilzer M, Roggel F, Gerbes AL. Role of Kupffer cells in host defense and liverdisease. Liver Int (2006) 26(10):1175-86. doi:10.1111/j.1478-3231.2006.01342.x
118. Lee WY, Moriarty TJ, Wong CH, Zhou H, Strieter RM, van Rooijen N, et al. An intravascular immune response to Borrelia burgdorferi involves Kupffer cells and iNKT cells. Nat Immunol (2010) 11(4):295-302. doi:10.1038/ni.1855
119. Gregory SH, Sagnimeni AJ, Wing EJ. Bacteria in the bloodstream are trapped in the liver and killed by immigrating neutrophils. J Immunol (1996) 157(6):2514-20
120. Huang LR, Wohlleber D, Reisinger F, Jenne CN, Cheng RL, Abdullah Z, et al. Intrahepatic myeloid-cell aggregates enable local proliferation of CD8(+) T cells and successful immunotherapy against chronic viral liver infection. Nat Immunol (2013) 14(6):574-83. doi:10.1038/ni.2573
121. Shi J, Gilbert GE, Kokubo Y, Ohashi T. Role of the liver in regulating numbers of circulating neutrophils. Blood (2001) 98(4):1226-30. doi:10.1182/blood.V98.4.1226
122. Grozovsky R, Hoffmeister KM, Falet H. Novel clearance mechanisms of platelets. Curr Opin Hematol (2010) 17(6):585-9. doi:10.1097/MOH.0b013e32833e7561
123. Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest (1998) 101(4):890-8. doi:10.1172/jci1112
124. Fuchs Y, Steller H. Programmed cell death in animal development and disease. Cell (2011) 147(4):742-58. doi:10.1016/j.cell.2011.10.033
125. Taylor RC, Cullen SP, Martin SJ. Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol (2008) 9(3):231-41. doi:10.1038/nrm2312
126. Hotchkiss RS, Osmon SB, Chang KC, Wagner TH, Coopersmith CM, Karl IE. Accelerated lymphocyte death in sepsis occurs by both the death receptor and mitochondrial pathways. J Immunol (2005) 174(8):5110-8. doi:10.4049/jimmunol.174.8.5110
127. Strasser A, Jost PJ, Nagata S. The many roles of FAS receptor signaling in the immune system. Immunity (2009) 30(2):180-92. doi:10.1016/j.immuni.2009.01.001
128. Lavrik IN, Krammer PH. Regulation of CD95/Fas signaling at the DISC. Cell Death Differ (2012) 19(1):36-41. doi:10.1038/cdd.2011.155
129. Dickens LS, Boyd RS, Jukes-Jones R, Hughes MA, Robinson GL, Fairall L, et al. A death effector domain chain DISC model reveals a crucial role for caspase-8 chain assembly in mediating apoptotic cell death. Mol Cell (2012) 47(2):291-305. doi:10.1016/j.molcel.2012.05.004
130. Xiong S, Mu T, Wang G, Jiang X. Mitochondria-mediated apoptosis in mammals. Protein Cell (2014) 5(10):737-49. doi:10.1007/s13238-014-0089-1
131. Galvin JP, Spaeny-Dekking LH, Wang B, Seth P, Hack CE, Froelich CJ. Apoptosis induced by granzyme B-glycosaminoglycan complexes: implications for granule-mediated apoptosis in vivo. J Immunol (1999) 162(9):5345-50
132. Huynh ML, Fadok VA, Henson PM. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest (2002) 109(1):41-50. doi:10.1172/jci11638
133. Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I. Immunosuppressive effects of apoptotic cells. Nature (1997) 390(6658):350-1. doi:10.1038/37022
134. Kushwah R, Wu J, Oliver JR, Jiang G, Zhang J, Siminovitch KA, et al. Uptake of apoptotic DC converts immature DC into tolerogenic DC that induce differentiation of Foxp3+ Treg. Eur J Immunol (2010) 40(4):1022-35. doi:10.1002/eji.200939782
135. Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA (2011) 306(23):2594-605. doi:10.1001/jama.2011.1829
136. Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, et al. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med (1999) 27(7):1230-51. doi:10.1097/00003246-199907000-00002
137. Hotchkiss RS, Tinsley KW, Swanson PE, Grayson MH, Osborne DF, Wagner TH, et al. Depletion of dendritic cells, but not macrophages, in patients with sepsis. J Immunol (2002) 168(5):2493-500. doi:10.4049/jimmunol.168.5.2493
138. Chung KP, Chang HT, Lo SC, Chang LY, Lin SY, Cheng A, et al. Severe lymphopenia is associated with elevated plasma interleukin-15 levels and increased mortality during severe sepsis. Shock (2015) 43(6):569-75. doi:10.1097/shk.0000000000000347
139. Drewry AM, Samra N, Skrupky LP, Fuller BM, Compton SM, Hotchkiss RS. Persistent lymphopenia after diagnosis of sepsis predicts mortality. Shock (2014) 42(5):383-91. doi:10.1097/shk.0000000000000234
140. Kaczmarek A, Vandenabeele P, Krysko DV. Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity (2013) 38(2):209-23. doi:10.1016/j.immuni.2013.02.003
141. Upton JW, Kaiser WJ, Mocarski ES. DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA. Cell Host Microbe (2012) 11(3):290-7. doi:10.1016/j.chom.2012.01.016
142. Kaiser WJ, Upton JW, Mocarski ES. Viral modulation of programmed necrosis. Curr Opin Virol (2013) 3(3):296-306. doi:10.1016/j.coviro.2013.05.019
143. Kayagaki N, Stowe IB, Lee BL, O'Rourke K, Anderson K, Warming S, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature (2015) 526(7575):666-71. doi:10.1038/nature15541
144. Jorgensen I, Zhang Y, Krantz BA, Miao EA. Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis. J Exp Med (2016) 213(10):2113-28. doi:10.1084/jem.20151613
145. Festjens N, Vanden Berghe T, Vandenabeele P. Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response. Biochim Biophys Acta (2006) 1757(9-10):1371-87. doi:10.1016/j.bbabio.2006.06.014
146. Lockshin RA, Zakeri Z. Cell death in health and disease. J Cell Mol Med (2007) 11(6):1214-24. doi:10.1111/j.1582-4934.2007.00150.x
147. He S, Wang L, Miao L, Wang T, Du F, Zhao L, et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell (2009) 137(6):1100-11. doi:10.1016/j.cell.2009.05.021
148. Cookson BT, Brennan MA. Pro-inflammatory programmed cell death. Trends Microbiol (2001) 9(3):113-4. doi:10.1016/S0966-842X(00)01936-3
149. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA (2016) 315(8):801-10. doi:10.1001/jama.2016.0287
150. Flick MJ, Du X, Witte DP, Jirouskova M, Soloviev DA, Busuttil SJ, et al. Leukocyte engagement of fibrin(ogen) via the integrin receptor alphaMbeta2/Mac-1 is critical for host inflammatory response in vivo. J Clin Invest (2004) 113(11):1596-606. doi:10.1172/jci20741
151. Luo D, Szaba FM, Kummer LW, Plow EF, Mackman N, Gailani D, et al. Protective roles for fibrin, tissue factor, plasminogen activator inhibitor-1, and thrombin activatable fibrinolysis inhibitor, but not factor XI, during defense against the Gram-negative bacterium Yersinia enterocolitica. J Immunol (2011) 187(4):1866-76. doi:10.4049/jimmunol.1101094
152. Opal SM, Esmon CT. Bench-to-bedside review: functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis. Crit Care (2003) 7(1):23-38. doi:10.1186/cc2219
153. Gando S, Levi M, Toh CH. Disseminated intravascular coagulation. Nat Rev Dis Primers (2016) 2:16037. doi:10.1038/nrdp.2016.37
154. Ogura H, Gando S, Saitoh D, Takeyama N, Kushimoto S, Fujishima S, et al. Epidemiology of severe sepsis in Japanese intensive care units: a prospective multicenter study. J Infect Chemother (2014) 20(3):157-62. doi:10.1016/j.jiac.2013.07.006
155. Levi M, van der Poll T. Coagulation and sepsis. Thromb Res (2017) 149:38-44. doi:10.1016/j.thromres.2016.11.007
156. Bengtson A, Heideman M. Anaphylatoxin formation in sepsis. Arch Surg (1988) 123(5):645-9. doi:10.1001/archsurg.1988.01400290131023
157. Nakae H, Endo S, Inada K, Yoshida M. Chronological changes in the complement system in sepsis. Surg Today (1996) 26(4):225-9. doi:10.1007/BF00311579
158. Ward PA. The dark side of C5a in sepsis. Nat Rev Immunol (2004) 4(2):133-42. doi:10.1038/nri1269
159. Yan C, Gao H. New insights for C5a and C5a receptors in sepsis. Front Immunol (2012) 3:368. doi:10.3389/fimmu.2012.00368
160. Niederbichler AD, Hoesel LM, Westfall MV, Gao H, Ipaktchi KR, Sun L, et al. An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction. J Exp Med (2006) 203(1):53-61. doi:10.1084/jem.20051207
161. Guo RF, Riedemann NC, Bernacki KD, Sarma VJ, Laudes IJ, Reuben JS, et al. Neutrophil C5a receptor and the outcome in a rat model of sepsis. FASEB J (2003) 17(13):1889-91. doi:10.1096/fj.03-0009fje
162. Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang M, Mackay CR, et al. Functional roles for C5a receptors in sepsis. Nat Med (2008) 14(5):551-7. doi:10.1038/nm1753
163. Chen NJ, Mirtsos C, Suh D, Lu YC, Lin WJ, McKerlie C, et al. C5L2 is critical for the biological activities of the anaphylatoxins C5a and C3a. Nature (2007) 446(7132):203-7. doi:10.1038/nature05559
164. Wright HL, Thomas HB, Moots RJ, Edwards SW. RNA-seq reveals activation of both common and cytokine-specific pathways following neutrophil priming. PLoS One (2013) 8(3):e58598. doi:10.1371/journal.pone.0058598
165. DeLeo FR, Renee J, McCormick S, Nakamura M, Apicella M, Weiss JP, et al. Neutrophils exposed to bacterial lipopolysaccharide upregulate NADPH oxidase assembly. J Clin Invest (1998) 101(2):455-63. doi:10.1172/jci949
166. Wrann CD, Winter SW, Barkhausen T, Hildebrand F, Krettek C, Riedemann NC. Distinct involvement of p38-, ERK1/2 and PKC signaling pathways in C5a-mediated priming of oxidative burst in phagocytic cells. Cell Immunol (2007) 245(2):63-9. doi:10.1016/j.cellimm.2007.04.001
167. Babior BM. Phagocytes and oxidative stress. Am J Med (2000) 109(1):33-44. doi:10.1016/S0002-9343(00)00481-2
168. Gupta AK, Joshi MB, Philippova M, Erne P, Hasler P, Hahn S, et al. Activated endothelial cells induce neutrophil extracellular traps and are susceptible to NETosis-mediated cell death. FEBS Lett (2010) 584(14):3193-7. doi:10.1016/j.febslet.2010.06.006
169. Delabranche X, Stiel L, Severac F, Galoisy AC, Mauvieux L, Zobairi F, et al. Evidence of netosis in septic shock-induced disseminated intravascular coagulation. Shock (2017) 47(3):313-7. doi:10.1097/shk.0000000000000719
170. Czaikoski PG, Mota JM, Nascimento DC, Sonego F, Castanheira FV, Melo PH, et al. Neutrophil extracellular traps induce organ damage during experimental and clinical sepsis. PLoS One (2016) 11(2):e0148142. doi:10.1371/journal.pone.0148142
171. Johansson PI, Windelov NA, Rasmussen LS, Sorensen AM, Ostrowski SR. Blood levels of histone-complexed DNA fragments are associated with coagulopathy, inflammation and endothelial damage early after trauma. J Emerg Trauma Shock (2013) 6(3):171-5. doi:10.4103/0974-2700.115327
172. Xu J, Zhang X, Pelayo R, Monestier M, Ammollo CT, Semeraro F, et al. Extracellular histones are major mediators of death in sepsis. Nat Med (2009) 15(11):1318-21. doi:10.1038/nm.2053
173. Meirow Y, Kanterman J, Baniyash M. Paving the road to tumor development and spreading: myeloid-derived suppressor cells are ruling the fate. Front Immunol (2015) 6:523. doi:10.3389/fimmu.2015.00523
174. Crook KR, Liu P. Role of myeloid-derived suppressor cells in autoimmune disease. World J Immunol (2014) 4(1):26-33. doi:10.5411/wji.v4.i1.26
175. Ezernitchi AV, Vaknin I, Cohen-Daniel L, Levy O, Manaster E, Halabi A, et al. TCR zeta down-regulation under chronic inflammation is mediated by myeloid suppressor cells differentially distributed between various lymphatic organs. J Immunol (2006) 177(7):4763-72. doi:10.4049/jimmunol.177.7.4763
176. Bunt SK, Yang L, Sinha P, Clements VK, Leips J, Ostrand-Rosenberg S. Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression. Cancer Res (2007) 67(20):10019-26. doi:10.1158/0008-5472.can-07-2354
177. Joo YD, Lee SM, Lee SW, Lee WS, Lee SM, Park JK, et al. Granulocyte colony-stimulating factor-induced immature myeloid cells inhibit acute graft-versus-host disease lethality through an indoleamine dioxygenase-independent mechanism. Immunology (2009) 128(1 Suppl):e632-40. doi:10.1111/j.1365-2567.2009.03048.x
178. Serafini P, Carbley R, Noonan KA, Tan G, Bronte V, Borrello I. High-dose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells. Cancer Res (2004) 64(17):6337-43. doi:10.1158/0008-5472.can-04-0757
179. Gabrilovich D, Ishida T, Oyama T, Ran S, Kravtsov V, Nadaf S, et al. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood (1998) 92(11):4150-66
180. Zhu X, Pribis JP, Rodriguez PC, Morris SM Jr, Vodovotz Y, Billiar TR, et al. The central role of arginine catabolism in T-cell dysfunction and increased susceptibility to infection after physical injury. Ann Surg (2014) 259(1):171-8. doi:10.1097/SLA.0b013e31828611f8
181. Darcy CJ, Minigo G, Piera KA, Davis JS, McNeil YR, Chen Y, et al. Neutrophils with myeloid derived suppressor function deplete arginine and constrain T cell function in septic shock patients. Crit Care (2014) 18(4):R163. doi:10.1186/cc14003
182. Vaknin I, Blinder L, Wang L, Gazit R, Shapira E, Genina O, et al. A common pathway mediated through Toll-like receptors leads to T-and natural killer-cell immunosuppression. Blood (2008) 111(3):1437-47. doi:10.1182/blood-2007-07-100404
183. Sander LE, Sackett SD, Dierssen U, Beraza N, Linke RP, Muller M, et al. Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function. J Exp Med (2010) 207(7):1453-64. doi:10.1084/jem.20091474
184. Janols H, Bergenfelz C, Allaoui R, Larsson AM, Ryden L, Bjornsson S, et al. A high frequency of MDSCs in sepsis patients, with the granulocytic subtype dominating in Gram-positive cases. J Leukoc Biol (2014) 96(5):685-93. doi:10.1189/jlb.5HI0214-074R
185. Hotchkiss RS, Moldawer LL. Parallels between cancer and infectious disease. N Engl J Med (2014) 371(4):380-3. doi:10.1056/NEJMcibr1404664
186. Mira JC, Cuschieri J, Ozrazgat-Baslanti T, Wang Z, Ghita GL, Loftus TJ, et al. The epidemiology of chronic critical illness after severe traumatic injury at two-level one trauma centers. Crit Care Med (2017) 45(12):1989-96. doi:10.1097/ccm.0000000000002697
187. Loftus TJ, Mira JC, Ozrazgat-Baslanti T, Ghita GL, Wang Z, Stortz JA, et al. Sepsis and critical illness research center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients. BMJ Open (2017) 7(7):e015136. doi:10.1136/bmjopen-2016-015136
188. Rosenthal MD, Moore FA. Persistent inflammatory, immunosuppressed, catabolic syndrome (PICS): a new phenotype of multiple organ failure. J Adv Nut Hum Metab (2015) 1(1):e784. doi:10.14800/janhm.784
189. Yang N, Li B, Ye B, Ke L, Chen F, Lu G, et al. The long-term quality of life in patients with persistent inflammation-immunosuppression and catabolism syndrome after severe acute pancreatitis: a retrospective cohort study. J Crit Care (2017) 42:101-6. doi:10.1016/j.jcrc.2017.07.013
190. Needham DM, Davidson J, Cohen H, Hopkins RO, Weinert C, Wunsch H, et al. Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders' conference. Crit Care Med (2012) 40(2):502-9. doi:10.1097/CCM.0b013e318232da75
191. Pugh AM, Auteri NJ, Goetzman HS, Caldwell CC, Nomellini V. A murine model of persistent inflammation, immune suppression, and catabolism syndrome. Int J Mol Sci (2017) 18(8):E1741. doi:10.3390/ijms18081741
192. Stortz JA, Raymond SL, Mira JC, Moldawer LL, Mohr AM, Efron PA. Murine models of sepsis and trauma: can we bridge the gap? ILAR J (2017) 58(1):90-105. doi:10.1093/ilar/ilx007
193. Efron PA, Mohr AM, Moore FA, Moldawer LL. The future of murine sepsis and trauma research models. J Leukoc Biol (2015) 98(6):945-52. doi:10.1189/jlb.5MR0315-127R
194. Brummel NE, Balas MC, Morandi A, Ferrante LE, Gill TM, Ely EW. Understanding and reducing disability in older adults following critical illness. Crit Care Med (2015) 43(6):1265-75. doi:10.1097/CCM.0000000000000924
195. Baldwin MR. Measuring and predicting long-term outcomes in older survivors of critical illness. Minerva Anestesiol (2015) 81(6):650-61
196. Hazeldine J, Lord JM, Hampson P. Immunesenescence and inflammaging: a contributory factor in the poor outcome of the geriatric trauma patient. Ageing Res Rev (2015) 24(Pt B):349-57. doi:10.1016/j.arr.2015.10.003
197. Olivieri F, Rippo MR, Monsurro V, Salvioli S, Capri M, Procopio AD, et al. MicroRNAs linking inflamm-aging, cellular senescence and cancer. Ageing Res Rev (2013) 12(4):1056-68. doi:10.1016/j.arr.2013.05.001
198. Kumar G, Kumar N, Taneja A, Kaleekal T, Tarima S, McGinley E, et al. Nationwide trends of severe sepsis in the 21st century (2000-2007). Chest (2011) 140(5):1223-31. doi:10.1378/chest.11-0352
199. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med (2003) 348(16):1546-54. doi:10.1056/NEJMoa022139
200. Kang SC, Matsutani T, Choudhry MA, Schwacha MG, Rue LW, Bland KI, et al. Are the immune responses different in middle-aged and young mice following bone fracture, tissue trauma and hemorrhage? Cytokine (2004) 26(5):223-30. doi:10.1016/j.cyto.2004.03.005
201. Moore FA, Sauaia A, Moore EE, Haenel JB, Burch JM, Lezotte DC. Postinjury multiple organ failure: a bimodal phenomenon. J Trauma (1996) 40(4):501-10; discussion 10-2. doi:10.1097/00005373-199604000-00001
202. Kozar RA, Arbabi S, Stein DM, Shackford SR, Barraco RD, Biffl WL, et al. Injury in the aged: geriatric trauma care at the crossroads. J Trauma Acute Care Surg (2015) 78(6):1197-209. doi:10.1097/TA.0000000000000656
203. Vanzant EL, Hilton RE, Lopez CM, Zhang J, Ungaro RF, Gentile LF, et al. Advanced age is associated with worsened outcomes and a unique genomic response in severely injured patients with hemorrhagic shock. Crit Care (2015) 19:77. doi:10.1186/s13054-015-0788-x
204. Martin GS, Mannino DM, Moss M. The effect of age on the development and outcome of adult sepsis. Crit Care Med (2006) 34(1):15-21. doi:10.1097/01.CCM.0000194535.82812.BA
205. Weng NP. Aging of the immune system: how much can the adaptive immune system adapt? Immunity (2006) 24(5):495-9. doi:10.1016/j.immuni.2006.05.001
206. Solana R, Pawelec G, Tarazona R. Aging and innate immunity. Immunity (2006) 24(5):491-4. doi:10.1016/j.immuni.2006.05.003
207. Suzuki K, Inoue S, Kametani Y, Komori Y, Chiba S, Sato T, et al. Reduced immunocompetent B cells and increased secondary infection in elderly patients with severe sepsis. Shock (2016) 46(3):270-8. doi:10.1097/SHK.0000000000000619
208. Nomellini V, Kaplan LJ, Sims CA, Caldwell CC. Chronic critical illness and persistent inflammation: what can we learn from the elderly, injured, septic, and malnourished? Shock (2018) 49(1):4-14. doi:10.1097/shk.0000000000000939
209. Delano MJ, Thayer T, Gabrilovich S, Kelly-Scumpia KM, Winfield RD, Scumpia PO, et al. Sepsis induces early alterations in innate immunity that impact mortality to secondary infection. J Immunol (2011) 186(1):195-202. doi:10.4049/jimmunol.1002104
210. Dykstra B, Olthof S, Schreuder J, Ritsema M, de Haan G. Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells. J Exp Med (2011) 208(13):2691-703. doi:10.1084/jem.20111490
211. Guerrettaz LM, Johnson SA, Cambier JC. Acquired hematopoietic stem cell defects determine B-cell repertoire changes associated with aging. Proc Natl Acad Sci U S A (2008) 105(33):11898-902. doi:10.1073/pnas.0805498105
212. Williams MD, Braun LA, Cooper LM, Johnston J, Weiss RV, Qualy RL, et al. Hospitalized cancer patients with severe sepsis: analysis of incidence, mortality, and associated costs of care. Crit Care (2004) 8(5):R291-8. doi:10.1186/cc2893
213. White MC, Holman DM, Boehm JE, Peipins LA, Grossman M, Henley SJ. Age and cancer risk: a potentially modifiable relationship. Am J Prev Med (2014) 46(3 Suppl 1):S7-15. doi:10.1016/j.amepre.2013.10.029
214. Palmer S, Albergante L, Blackburn CC, Newman TJ. Thymic involution and rising disease incidence with age. Proc Natl Acad Sci U S A (2018) 115(8):1883-8. doi:10.1073/pnas.1714478115
215. Goldszmid RS, Dzutsev A, Trinchieri G. Host immune response to infection and cancer: unexpected commonalities. Cell Host Microbe (2014) 15(3):295-305. doi:10.1016/j.chom.2014.02.003
216. Pietras EM, Warr MR, Passegue E. Cell cycle regulation in hematopoietic stem cells. J Cell Biol (2011) 195(5):709-20. doi:10.1083/jcb.201102131
217. Boettcher S, Ziegler P, Schmid MA, Takizawa H, van Rooijen N, Kopf M, et al. Cutting edge: LPS-induced emergency myelopoiesis depends on TLR4-expressing nonhematopoietic cells. J Immunol (2012) 188(12):5824-8. doi:10.4049/jimmunol.1103253
218. Boiko JR, Borghesi L. Hematopoiesis sculpted by pathogens: toll-like receptors and inflammatory mediators directly activate stem cells. Cytokine (2012) 57(1):1-8. doi:10.1016/j.cyto.2011.10.005
219. Baldridge MT, King KY, Goodell MA. Inflammatory signals regulate hematopoietic stem cells. Trends Immunol (2011) 32(2):57-65. doi:10.1016/j.it.2010.12.003
220. Nelson S, Belknap SM, Carlson RW, Dale D, DeBoisblanc B, Farkas S, et al. A randomized controlled trial of filgrastim as an adjunct to antibiotics for treatment of hospitalized patients with community-acquired pneumonia. CAP study group. J Infect Dis (1998) 178(4):1075-80. doi:10.1086/515694
221. Root RK, Lodato RF, Patrick W, Cade JF, Fotheringham N, Milwee S, et al. Multicenter, double-blind, placebo-controlled study of the use of filgrastim in patients hospitalized with pneumonia and severe sepsis. Crit Care Med (2003) 31(2):367-73. doi:10.1097/01.ccm.0000048629.32625.5d
222. Paine R III, Standiford TJ, Dechert RE, Moss M, Martin GS, Rosenberg AL, et al. A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury. Crit Care Med (2012) 40(1):90-7. doi:10.1097/CCM.0b013e31822d7bf0
223. Meisel C, Schefold JC, Pschowski R, Baumann T, Hetzger K, Gregor J, et al. Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial. Am J Respir Crit Care Med (2009) 180(7):640-8. doi:10.1164/rccm.200903-0363OC
224. Bo L, Wang F, Zhu J, Li J, Deng X. Granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) for sepsis: a meta-analysis. Crit Care (2011) 15(1):R58. doi:10.1186/cc10031
225. Hutchins NA, Unsinger J, Hotchkiss RS, Ayala A. The new normal: immunomodulatory agents against sepsis immune suppression. Trends Mol Med (2014) 20(4):224-33. doi:10.1016/j.molmed.2014.01.002
226. Unsinger J, Burnham CA, McDonough J, Morre M, Prakash PS, Caldwell CC, et al. Interleukin-7 ameliorates immune dysfunction and improves survival in a 2-hit model of fungal sepsis. J Infect Dis (2012) 206(4):606-16. doi:10.1093/infdis/jis383
227. Kasten KR, Prakash PS, Unsinger J, Goetzman HS, England LG, Cave CM, et al. Interleukin-7 (IL-7) treatment accelerates neutrophil recruitment through gamma delta T-cell IL-17 production in a murine model of sepsis. Infect Immun (2010) 78(11):4714-22. doi:10.1128/iai.00456-10
228. Inoue S, Unsinger J, Davis CG, Muenzer JT, Ferguson TA, Chang K, et al. IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis. J Immunol (2010) 184(3):1401-9. doi:10.4049/jimmunol.0902307
229. Nalos M, Santner-Nanan B, Parnell G, Tang B, McLean AS, Nanan R. Immune effects of interferon gamma in persistent staphylococcal sepsis. Am J Respir Crit Care Med (2012) 185(1):110-2. doi:10.1164/ajrccm.185.1.110
230. Chang KC, Burnham CA, Compton SM, Rasche DP, Mazuski RJ, McDonough JS, et al. Blockade of the negative co-stimulatory molecules PD-1 and CTLA-4 improves survival in primary and secondary fungal sepsis. Crit Care (2013) 17(3):R85. doi:10.1186/cc12711
231. Huang X, Venet F, Wang YL, Lepape A, Yuan Z, Chen Y, et al. PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis. Proc Natl Acad Sci U S A (2009) 106(15):6303-8. doi:10.1073/pnas.0809422106
232. Inoue S, Bo L, Bian J, Unsinger J, Chang K, Hotchkiss RS. Dose-dependent effect of anti-CTLA-4 on survival in sepsis. Shock (2011) 36(1):38-44. doi:10.1097/SHK.0b013e3182168cce
233. Yang X, Jiang X, Chen G, Xiao Y, Geng S, Kang C, et al. T cell Ig mucin-3 promotes homeostasis of sepsis by negatively regulating the TLR response. J Immunol (2013) 190(5):2068-79. doi:10.4049/jimmunol.1202661
234. Zhao Z, Jiang X, Kang C, Xiao Y, Hou C, Yu J, et al. Blockade of the T cell immunoglobulin and mucin domain protein 3 pathway exacerbates sepsis-induced immune deviation and immunosuppression. Clin Exp Immunol (2014) 178(2):279-91. doi:10.1111/cei.12401
235. Workman CJ, Wang Y, El Kasmi KC, Pardoll DM, Murray PJ, Drake CG, et al. LAG-3 regulates plasmacytoid dendritic cell homeostasis. J Immunol (2009) 182(4):1885-91. doi:10.4049/jimmunol.0800185
236. Durham NM, Nirschl CJ, Jackson CM, Elias J, Kochel CM, Anders RA, et al. Lymphocyte activation gene 3 (LAG-3) modulates the ability of CD4 T-cells to be suppressed in vivo. PLoS One (2014) 9(11):e109080. doi:10.1371/journal.pone.0109080
237. Wu J, Zhou L, Liu J, Ma G, Kou Q, He Z, et al. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Critical care (2013) 17(1):R8. doi:10.1186/cc11932
238. Wischmeyer PE, San-Millan I. Winning the war against ICU-acquired weakness: new innovations in nutrition and exercise physiology. Crit Care (2015) 19(Suppl 3):S6. doi:10.1186/cc14724
239. Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, et al. Acute skeletal muscle wasting in critical illness. JAMA (2013) 310(15):1591-600. doi:10.1001/jama.2013.278481
240. Moore FA, Phillips SM, McClain CJ, Patel JJ, Martindale RG. Nutrition support for persistent inflammation, immunosuppression, and catabolism syndrome. Nutr Clin Pract (2017) 32(1_suppl):121s-7s. doi:10.1177/0884533616687502
241. Bozzetti F, Arends J, Lundholm K, Micklewright A, Zurcher G, Muscaritoli M. ESPEN guidelines on parenteral nutrition: non-surgical oncology. Clin Nut (2009) 28(4):445-54. doi:10.1016/j.clnu.2009.04.011
242. Wolfe RR, Miller SL, Miller KB. Optimal protein intake in the elderly. Clin Nut (2008) 27(5):675-84. doi:10.1016/j.clnu.2008.06.008
243. Morley JE, Argiles JM, Evans WJ, Bhasin S, Cella D, Deutz NE, et al. Nutritional recommendations for the management of sarcopenia. J Am Med Dir Assoc (2010) 11(6):391-6. doi:10.1016/j.jamda.2010.04.014
244. Herndon DN, Tompkins RG. Support of the metabolic response to burn injury. Lancet (2004) 363(9424):1895-902. doi:10.1016/s0140-6736(04)16360-5
245. Wu G, Bazer FW, Davis TA, Kim SW, Li P, Marc Rhoads J, et al. Arginine metabolism and nutrition in growth, health and disease. Amino Acids (2009) 37(1):153-68. doi:10.1007/s00726-008-0210-y
246. Zea AH, Rodriguez PC, Culotta KS, Hernandez CP, DeSalvo J, Ochoa JB, et al. L-Arginine modulates CD3zeta expression and T cell function in activated human T lymphocytes. Cell Immunol (2004) 232(1-2):21-31. doi:10.1016/j.cellimm.2005.01.004
247. Schlegel L, Coudray-Lucas C, Barbut F, Le Boucher J, Jardel A, Zarrabian S, et al. Bacterial dissemination and metabolic changes in rats induced by endotoxemia following intestinal E. coli overgrowth are reduced by ornithine alpha-ketoglutarate administration. J Nutr (2000) 130(12):2897-902. doi:10.1093/jn/130.12.2897
248. English KL, Mettler JA, Ellison JB, Mamerow MM, Arentson-Lantz E, Pattarini JM, et al. Leucine partially protects muscle mass and function during bed rest in middle-aged adults. Am J Clin Nutr (2016) 103(2):465-73. doi:10.3945/ajcn.115.112359
249. Cerra FB, Siegel JH, Coleman B, Border JR, McMenamy RR. Septic autocannibalism. A failure of exogenous nutritional support. Ann Surg (1980) 192(4):570-80. doi:10.1097/00000658-198010000-00015
250. Hernandez-Garcia AD, Columbus DA, Manjarin R, Nguyen HV, Suryawan A, Orellana RA, et al. Leucine supplementation stimulates protein synthesis and reduces degradation signal activation in muscle of newborn pigs during acute endotoxemia. Am J Physiol Endocrinol Metab (2016) 311(4):E791-801. doi:10.1152/ajpendo.00217.2016
251. Cynober L, de Bandt JP, Moinard C. Leucine and citrulline: two major regulators of protein turnover. World Rev Nutr Diet (2013) 105:97-105. doi:10.1159/000341278
252. Hrynyk M, Neufeld RJ. Insulin and wound healing. Burns (2014) 40(8):1433-46. doi:10.1016/j.burns.2014.03.020
253. Herndon DN, Voigt CD, Capek KD, Wurzer P, Guillory A, Kline A, et al. Reversal of growth arrest with the combined administration of oxandrolone and propranolol in severely burned children. Ann Surg (2016) 264(3):421-8. doi:10.1097/sla.0000000000001844
254. Diaz EC, Herndon DN, Porter C, Sidossis LS, Suman OE, Borsheim E. Effects of pharmacological interventions on muscle protein synthesis and breakdown in recovery from burns. Burns (2015) 41(4):649-57. doi:10.1016/j.burns.2014.10.010
255. Kayambu G, Boots R, Paratz J. Physical therapy for the critically ill in the ICU: a systematic review and meta-analysis. Crit Care Med (2013) 41(6):1543-54. doi:10.1097/CCM.0b013e31827ca637
256. Cermak NM, Res PT, de Groot LC, Saris WH, van Loon LJ. Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis. Am J Clin Nutr (2012) 96(6):1454-64. doi:10.3945/ajcn.112.037556
257. Thaiss CA, Zmora N, Levy M, Elinav E. The microbiome and innate immunity. Nature (2016) 535(7610):65-74. doi:10.1038/nature18847
258. Khosravi A, Yanez A, Price JG, Chow A, Merad M, Goodridge HS, et al. Gut microbiota promote hematopoiesis to control bacterial infection. Cell Host Microbe (2014) 15(3):374-81. doi:10.1016/j.chom.2014.02.006
259. Zhang D, Chen G, Manwani D, Mortha A, Xu C, Faith JJ, et al. Neutrophil ageing is regulated by the microbiome. Nature (2015) 525(7570):528-32. doi:10.1038/nature15367
260. Shimizu K, Ogura H, Hamasaki T, Goto M, Tasaki O, Asahara T, et al. Altered gut flora are associated with septic complications and death in critically ill patients with systemic inflammatory response syndrome. Dig Dis Sci (2011) 56(4):1171-7. doi:10.1007/s10620-010-1418-8
261. Shimizu K, Ogura H, Asahara T, Nomoto K, Morotomi M, Nakahori Y, et al. Gastrointestinal dysmotility is associated with altered gut flora and septic mortality in patients with severe systemic inflammatory response syndrome: a preliminary study. Neurogastroenterol Motil (2011) 23(4):330-5, e157. doi:10.1111/j.1365-2982.2010.01653.x
262. Stecher B, Maier L, Hardt WD. 'Blooming' in the gut: how dysbiosis might contribute to pathogen evolution. Nat Rev Microbiol (2013) 11(4):277-84. doi:10.1038/nrmicro2989
263. Buffie CG, Bucci V, Stein RR, McKenney PT, Ling L, Gobourne A, et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature (2015) 517(7533):205-8. doi:10.1038/nature13828
264. Fan J, Li G, Wu L, Tao S, Wang W, Sheng Z, et al. Parenteral glutamine supplementation in combination with enteral nutrition improves intestinal immunity in septic rats. Nutrition (2015) 31(5):766-74. doi:10.1016/j.nut.2014.11.021
265. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med (2013) 368(5):407-15. doi:10.1056/NEJMoa1205037
266. Zaborin A, Defazio JR, Kade M, Kaiser BL, Belogortseva N, Camp DG II, et al. Phosphate-containing polyethylene glycol polymers prevent lethal sepsis by multidrug-resistant pathogens. Antimicrob Agents Chemother (2014) 58(2):966-77. doi:10.1128/aac.02183-13
267. Christaki E, Giamarellos-Bourboulis EJ. The beginning of personalized medicine in sepsis: small steps to a bright future. Clin Genet (2014) 86(1):56-61. doi:10.1111/cge.12368
268. Wang L, Ko ER, Gilchrist JJ, Pittman KJ, Rautanen A, Pirinen M, et al. Human genetic and metabolite variation reveals that methylthioadenosine is a prognostic biomarker and an inflammatory regulator in sepsis. Sci Adv (2017) 3(3):e1602096. doi:10.1126/sciadv.1602096
269. Burnham KL, Davenport EE, Radhakrishnan J, Humburg P, Gordon AC, Hutton P, et al. Shared and distinct aspects of the sepsis transcriptomic response to fecal peritonitis and pneumonia. Am J Respir Crit Care Med (2017) 196(3):328-39. doi:10.1164/rccm.201608-1685OC
270. Cuenca AG, Gentile LF, Lopez MC, Ungaro R, Liu H, Xiao W, et al. Development of a genomic metric that can be rapidly used to predict clinical outcome in severely injured trauma patients. Crit Care Med (2013) 41(5):1175-85. doi:10.1097/CCM.0b013e318277131c
271. LeCun Y, Bengio Y, Hinton G. Deep learning. Nature (2015) 521(7553):436-44. doi:10.1038/nature14539
272. Tsoukalas A, Albertson T, Tagkopoulos I. From data to optimal decision making: a data-driven, probabilistic machine learning approach to decision support for patients with sepsis. JMIR Med Inform (2015) 3(1):e11. doi:10.2196/medinform.3445