MyD88-dependent inflammasome activation and autophagy inhibition contributes to Ehrlichia-induced liver injury and toxic shock

PLoS Pathogens

Volumn 13, Issue 10, 2017, Pages

  Kader, Muhamuda ^a   Alaoui EL Azher, Mounia ^a   Vorhauer, Jennie ^a   Kode, Bhushan B ^a   Wells, Jakob Z ^a   Stolz, Donna ^a   Michalopoulos, George ^a,b   Wells, Alan ^a,b   Scott, Melanie ^b   Ismail, Nahed ^a,b  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BAFILOMYCIN A1; CASPASE 11; CD69 ANTIGEN; CRYOPYRIN; INFLAMMASOME; INTERFERON; INTERLEUKIN 10; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; LACTATE DEHYDROGENASE; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MYELOID DIFFERENTIATION FACTOR 88; PATTERN RECOGNITION RECEPTOR; PHOSPHOTRANSFERASE; RAPAMYCIN; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 9; TUMOR NECROSIS FACTOR; MYD88 PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOPHAGY; AUTOPHAGY INHIBITION; BACTERIAL CLEARANCE; BACTERIAL LOAD; BONE MARROW DERIVED MACROPHAGE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL ACTIVATION; CELL DIVISION; CONFOCAL MICROSCOPY; CONTROLLED STUDY; EHRLICHIOSIS; ENZYME LINKED IMMUNOSORBENT ASSAY; EXPERIMENTAL LIVER INJURY; FEMALE; FLOW CYTOMETRY; HISTOPATHOLOGY; IMMUNOBLOTTING; IMMUNOFLUORESCENCE TEST; IMMUNOPATHOLOGY; LIVER INJURY; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOPHAGY; MOUSE; NONHUMAN; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA EXTRACTION; TOXIC SHOCK SYNDROME; TRANSMISSION ELECTRON MICROSCOPY; TUNEL ASSAY; WESTERN BLOTTING; ACUTE LIVER FAILURE; ANIMAL; C57BL MOUSE; DISEASE MODEL; EHRLICHIA; FLUORESCENT ANTIBODY TECHNIQUE; IMAGE PROCESSING; IMMUNOLOGY; KNOCKOUT MOUSE; METABOLISM; MICROBIOLOGY; SEPTIC SHOCK;

ANIMALS; AUTOPHAGY; BLOTTING, WESTERN; DISEASE MODELS, ANIMAL; EHRLICHIA; EHRLICHIOSIS; ENZYME-LINKED IMMUNOSORBENT ASSAY; FEMALE; FLOW CYTOMETRY; FLUORESCENT ANTIBODY TECHNIQUE; IMAGE PROCESSING, COMPUTER-ASSISTED; IN SITU NICK-END LABELING; INFLAMMASOMES; LIVER FAILURE, ACUTE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICROSCOPY, CONFOCAL; MICROSCOPY, ELECTRON, TRANSMISSION; MYELOID DIFFERENTIATION FACTOR 88; REAL-TIME POLYMERASE CHAIN REACTION; SHOCK, SEPTIC;

EID: 85032643791     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1006644     Document Type: Article

References (78)

1. Bitsaktsis C, Huntington J, Winslow G, Production of IFN-gamma by CD4 T cells is essential for resolving ehrlichia infection. Journal of immunology (Baltimore, Md: 1950). 2004;172(11):6894–901. Epub 2004/05/22. 15153508.
2. Nandi B, Chatterjee M, Hogle K, McLaughlin M, MacNamara K, Racine R, et al. Antigen display, T-cell activation, and immune evasion during acute and chronic ehrlichiosis. Infection and immunity. 2009;77(10):4643–53. Epub 2009/07/29. doi: 10.1128/IAI.01433-08 19635826; PubMed Central PMCID: PMCPMC2747950.
3. Ismail N, Soong L, McBride JW, Valbuena G, Olano JP, Feng HM, et al. Overproduction of TNF-alpha by CD8+ type 1 cells and down-regulation of IFN-gamma production by CD4+ Th1 cells contribute to toxic shock-like syndrome in an animal model of fatal monocytotropic ehrlichiosis. Journal of immunology (Baltimore, Md: 1950). 2004;172(3):1786–800. Epub 2004/01/22. 14734762.
4. Stevenson HL, Jordan JM, Peerwani Z, Wang HQ, Walker DH, Ismail N, An intradermal environment promotes a protective type-1 response against lethal systemic monocytotropic ehrlichial infection. Infection and immunity. 2006;74(8):4856–64. Epub 2006/07/25. doi: 10.1128/IAI.00246-06 16861674; PubMed Central PMCID: PMCPMC1539596.
5. de Sousa R, Ismail N, Doria-Nobrega S, Costa P, Abreu T, Franca A, et al. The presence of eschars, but not greater severity, in Portuguese patients infected with Israeli spotted fever. Annals of the New York Academy of Sciences. 2005;1063:197–202. Epub 2006/02/17. doi: 10.1196/annals.1355.032 16481514.
6. Ismail N, Stevenson HL, Walker DH, Role of tumor necrosis factor alpha (TNF-alpha) and interleukin-10 in the pathogenesis of severe murine monocytotropic ehrlichiosis: increased resistance of TNF receptor p55- and p75-deficient mice to fatal ehrlichial infection. Infection and immunity. 2006;74(3):1846–56. Epub 2006/02/24. doi: 10.1128/IAI.74.3.1846-1856.2006 16495559; PubMed Central PMCID: PMCPMC1418656.
7. Stevenson HL, Estes MD, Thirumalapura NR, Walker DH, Ismail N, Natural killer cells promote tissue injury and systemic inflammatory responses during fatal Ehrlichia-induced toxic shock-like syndrome. The American journal of pathology. 2010;177(2):766–76. Epub 2010/07/10. doi: 10.2353/ajpath.2010.091110 20616341; PubMed Central PMCID: PMCPMC2913354.
8. Chattoraj P, Yang Q, Khandai A, Al-Hendy O, Ismail N, TLR2 and Nod2 mediate resistance or susceptibility to fatal intracellular Ehrlichia infection in murine models of ehrlichiosis. PloS one. 2013;8(3):e58514. Epub 2013/03/26. doi: 10.1371/journal.pone.0058514 23526993; PubMed Central PMCID: PMCPMC3602367.
9. Aachoui Y, Leaf IA, Hagar JA, Fontana MF, Campos CG, Zak DE, et al. Caspase-11 protects against bacteria that escape the vacuole. Science (New York, NY). 2013;339(6122):975–8. Epub 2013/01/26. doi: 10.1126/science.1230751 23348507; PubMed Central PMCID: PMCPMC3697099.
10. Anand PK, Malireddi RK, Kanneganti TD, Role of the nlrp3 inflammasome in microbial infection. Frontiers in microbiology. 2011;2:12. Epub 2011/06/21. doi: 10.3389/fmicb.2011.00012 21687408; PubMed Central PMCID: PMCPMC3109351.
11. Broz P, Monack DM, Noncanonical inflammasomes: caspase-11 activation and effector mechanisms. PLoS pathogens. 2013;9(2):e1003144. Epub 2013/03/08. doi: 10.1371/journal.ppat.1003144 23468620; PubMed Central PMCID: PMCPMC3585133.
12. Hagar JA, Miao EA, Detection of cytosolic bacteria by inflammatory caspases. Current opinion in microbiology. 2014;17:61–6. Epub 2014/03/04. doi: 10.1016/j.mib.2013.11.008 24581694; PubMed Central PMCID: PMCPMC3942666.
13. Kanneganti TD, Lamkanfi M, Nunez G, Intracellular NOD-like receptors in host defense and disease. Immunity. 2007;27(4):549–59. Epub 2007/10/31. doi: 10.1016/j.immuni.2007.10.002 17967410.
14. Bast A, Krause K, Schmidt IH, Pudla M, Brakopp S, Hopf V, et al. Caspase-1-dependent and -independent cell death pathways in Burkholderia pseudomallei infection of macrophages. PLoS pathogens. 2014;10(3):e1003986. Epub 2014/03/15. doi: 10.1371/journal.ppat.1003986 24626296; PubMed Central PMCID: PMCPMC3953413.
15. Casson CN, Copenhaver AM, Zwack EE, Nguyen HT, Strowig T, Javdan B, et al. Caspase-11 activation in response to bacterial secretion systems that access the host cytosol. PLoS pathogens. 2013;9(6):e1003400. Epub 2013/06/14. doi: 10.1371/journal.ppat.1003400 23762026; PubMed Central PMCID: PMCPMC3675167.
16. Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H, et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature. 2016;535(7610):153–8. Epub 2016/07/08. doi: 10.1038/nature18629 27383986.
17. Croker BA, O'Donnell JA, Gerlic M, Pyroptotic death storms and cytopenia. Current opinion in immunology. 2014;26:128–37. Epub 2014/02/22. doi: 10.1016/j.coi.2013.12.002 24556409.
18. Broz P, Ruby T, Belhocine K, Bouley DM, Kayagaki N, Dixit VM, et al. Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1. Nature. 2012;490(7419):288–91. doi: 10.1038/nature11419 22895188; PubMed Central PMCID: PMC3470772.
19. Pilla DM, Hagar JA, Haldar AK, Mason AK, Degrandi D, Pfeffer K, et al. Guanylate binding proteins promote caspase-11-dependent pyroptosis in response to cytoplasmic LPS. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(16):6046–51. Epub 2014/04/10. doi: 10.1073/pnas.1321700111 24715728; PubMed Central PMCID: PMCPMC4000848.
20. Anand PK, Malireddi RK, Lukens JR, Vogel P, Bertin J, Lamkanfi M, et al. NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature. 2012;488(7411):389–93. Epub 2012/07/06. doi: 10.1038/nature11250 22763455; PubMed Central PMCID: PMCPMC3422416.
21. Kayagaki N, Wong MT, Stowe IB, Ramani SR, Gonzalez LC, Akashi-Takamura S, et al. Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science (New York, NY). 2013;341(6151):1246–9. Epub 2013/07/28. doi: 10.1126/science.1240248 23887873.
22. Matusiak M, Van Opdenbosch N, Vande Walle L, Sirard JC, Kanneganti TD, Lamkanfi M, Flagellin-induced NLRC4 phosphorylation primes the inflammasome for activation by NAIP5. Proceedings of the National Academy of Sciences of the United States of America. 2015;112(5):1541–6. Epub 2015/01/22. doi: 10.1073/pnas.1417945112 25605939; PubMed Central PMCID: PMCPMC4321312.
23. Ghose P, Ali AQ, Fang R, Forbes D, Ballard B, Ismail N, The interaction between IL-18 and IL-18 receptor limits the magnitude of protective immunity and enhances pathogenic responses following infection with intracellular bacteria. Journal of immunology (Baltimore, Md: 1950). 2011;187(3):1333–46. Epub 2011/07/01. doi: 10.4049/jimmunol.1100092 21715688; PubMed Central PMCID: PMCPMC3140540.
24. Yang Q, Stevenson HL, Scott MJ, Ismail N, Type I Interferon Contributes to Noncanonical Inflammasome Activation, Mediates Immunopathology, and Impairs Protective Immunity during Fatal Infection with Lipopolysaccharide-Negative Ehrlichiae. The American journal of pathology. 2014. Epub 2014/12/08. doi: 10.1016/j.ajpath.2014.10.005 25481711.
25. Ismail N, Crossley EC, Stevenson HL, Walker DH, Relative importance of T-cell subsets in monocytotropic ehrlichiosis: a novel effector mechanism involved in Ehrlichia-induced immunopathology in murine ehrlichiosis. Infection and immunity. 2007;75(9):4608–20. Epub 2007/06/15. doi: 10.1128/IAI.00198-07 17562770; PubMed Central PMCID: PMCPMC1951155.
26. Yang Q, Ghose P, Ismail N, Neutrophils mediate immunopathology and negatively regulate protective immune responses during fatal bacterial infection-induced toxic shock. Infection and immunity. 2013;81(5):1751–63. Epub 2013/03/13. doi: 10.1128/IAI.01409-12 23478316; PubMed Central PMCID: PMCPMC3647993.
27. Deretic V, Saitoh T, Akira S, Autophagy in infection, inflammation and immunity. Nature reviews Immunology. 2013;13(10):722–37. Epub 2013/09/26. doi: 10.1038/nri3532 24064518.
28. Latz E, Xiao TS, Stutz A, Activation and regulation of the inflammasomes. Nature reviews Immunology. 2013;13(6):397–411. doi: 10.1038/nri3452 23702978; PubMed Central PMCID: PMC3807999.
29. Guarda G, Braun M, Staehli F, Tardivel A, Mattmann C, Forster I, et al. Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity. 2011;34(2):213–23. Epub 2011/02/26. doi: 10.1016/j.immuni.2011.02.006 21349431.
30. Henry T, Brotcke A, Weiss DS, Thompson LJ, Monack DM, Type I interferon signaling is required for activation of the inflammasome during Francisella infection. The Journal of experimental medicine. 2007;204(5):987–94. Epub 2007/04/25. doi: 10.1084/jem.20062665 17452523; PubMed Central PMCID: PMCPMC2118578.
31. Malireddi RK, Kanneganti TD, Role of type I interferons in inflammasome activation, cell death, and disease during microbial infection. Frontiers in cellular and infection microbiology. 2013;3:77. Epub 2013/11/26. doi: 10.3389/fcimb.2013.00077 24273750; PubMed Central PMCID: PMCPMC3824101.
32. Zhang Y, Thai V, McCabe A, Jones M, MacNamara KC, Type I interferons promote severe disease in a mouse model of lethal ehrlichiosis. Infection and immunity. 2014;82(4):1698–709. Epub 2014/02/05. doi: 10.1128/IAI.01564-13 24491580; PubMed Central PMCID: PMCPMC3993392.
33. Fang R, Hara H, Sakai S, Hernandez-Cuellar E, Mitsuyama M, Kawamura I, et al. Type I interferon signaling regulates activation of the absent in melanoma 2 inflammasome during Streptococcus pneumoniae infection. Infection and immunity. 2014;82(6):2310–7. Epub 2014/03/20. doi: 10.1128/IAI.01572-14 24643540; PubMed Central PMCID: PMCPMC4019145.
34. Koppe U, Hogner K, Doehn JM, Muller HC, Witzenrath M, Gutbier B, et al. Streptococcus pneumoniae stimulates a STING- and IFN regulatory factor 3-dependent type I IFN production in macrophages, which regulates RANTES production in macrophages, cocultured alveolar epithelial cells, and mouse lungs. Journal of immunology (Baltimore, Md: 1950). 2012;188(2):811–7. Epub 2011/12/14. doi: 10.4049/jimmunol.1004143 22156592.
35. Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012;8(4):445–544. Epub 2012/09/12. doi: 10.4161/auto.19496 22966490; PubMed Central PMCID: PMCPMC3404883.
36. Kahrstrom CT, Host response: Salmonella triumphs over autophagy. Nature reviews Microbiology. 2012;10(8):519. Epub 2012/07/04. doi: 10.1038/nrmicro2835 22751484.
37. Lin M, Liu H, Xiong Q, Niu H, Cheng Z, Yamamoto A, et al. Ehrlichia secretes Etf-1 to induce autophagy and capture nutrients for its growth through RAB5 and class III phosphatidylinositol 3-kinase. Autophagy. 2016;12(11):2145–66. Epub 2016/11/02. doi: 10.1080/15548627.2016.1217369 27541856; PubMed Central PMCID: PMCPMC5103349.
38. Niu H, Xiong Q, Yamamoto A, Hayashi-Nishino M, Rikihisa Y, Autophagosomes induced by a bacterial Beclin 1 binding protein facilitate obligatory intracellular infection. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(51):20800–7. Epub 2012/12/01. doi: 10.1073/pnas.1218674109 23197835; PubMed Central PMCID: PMCPMC3529060.
39. Rikihisa Y, Anaplasma phagocytophilum and Ehrlichia chaffeensis: subversive manipulators of host cells. Nature reviews Microbiology. 2010;8(5):328–39. Epub 2010/04/08. doi: 10.1038/nrmicro2318 20372158.
40. Lee EH, Rikihisa Y, Absence of tumor necrosis factor alpha, interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor expression but presence of IL-1beta, IL-8, and IL-10 expression in human monocytes exposed to viable or killed Ehrlichia chaffeensis. Infection and immunity. 1996;64(10):4211–9. Epub 1996/10/01. 8926090; PubMed Central PMCID: PMCPMC174358.
41. Ismail N, Bloch KC, McBride JW, Human ehrlichiosis and anaplasmosis. Clinics in laboratory medicine. 2010;30(1):261–92. Epub 2010/06/02. doi: 10.1016/j.cll.2009.10.004 20513551; PubMed Central PMCID: PMCPMC2882064.
42. Rikihisa Y, Molecular Pathogenesis of Ehrlichia chaffeensis Infection. Annual review of microbiology. 2015;69:283–304. Epub 2015/10/22. doi: 10.1146/annurev-micro-091014-104411 26488275.
43. Trinchieri G, Sher A, Cooperation of Toll-like receptor signals in innate immune defence. Nature reviews Immunology. 2007;7(3):179–90. Epub 2007/02/24. doi: 10.1038/nri2038 17318230.
44. Olano JP, Wen G, Feng HM, McBride JW, Walker DH, Histologic, serologic, and molecular analysis of persistent ehrlichiosis in a murine model. The American journal of pathology. 2004;165(3):997–1006. Epub 2004/08/28. doi: 10.1016/S0002-9440(10)63361-5 15331423; PubMed Central PMCID: PMCPMC1618610.
45. Sotomayor EA, Popov VL, Feng HM, Walker DH, Olano JP, Animal model of fatal human monocytotropic ehrlichiosis. The American journal of pathology. 2001;158(2):757–69. Epub 2001/02/13. doi: 10.1016/S0002-9440(10)64018-7 11159213; PubMed Central PMCID: PMCPMC1850300.
46. Kanneganti TD, The inflammasome: firing up innate immunity. Immunological reviews. 2015;265(1):1–5. Epub 2015/04/17. doi: 10.1111/imr.12297 25879279; PubMed Central PMCID: PMCPMC4701203.
47. Man SM, Karki R, Kanneganti TD, Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunological reviews. 2017;277(1):61–75. Epub 2017/05/04. doi: 10.1111/imr.12534 28462526; PubMed Central PMCID: PMCPMC5416822.
48. Abdelaziz DH, Khalil H, Cormet-Boyaka E, Amer AO, The cooperation between the autophagy machinery and the inflammasome to implement an appropriate innate immune response: do they regulate each other?Immunological reviews. 2015;265(1):194–204. Epub 2015/04/17. doi: 10.1111/imr.12288 25879294; PubMed Central PMCID: PMCPMC4747236.
49. Man SM, Karki R, Briard B, Burton A, Gingras S, Pelletier S, et al. Differential roles of caspase-1 and caspase-11 in infection and inflammation. Scientific reports. 2017;7:45126. Epub 2017/03/28. doi: 10.1038/srep45126 28345580; PubMed Central PMCID: PMCPMC5366862.
50. Sun Q, Fan J, Billiar TR, Scott MJ, Inflammasome and autophagy regulation—a two-way street. Molecular medicine (Cambridge, Mass). 2017;23. Epub 2017/07/26. doi: 10.2119/molmed.2017.00077 28741645.
51. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016;12(1):1–222. Epub 2016/01/23. doi: 10.1080/15548627.2015.1100356 26799652; PubMed Central PMCID: PMCPMC4835977.
52. Dunphy PS, Luo T, McBride JW, Ehrlichia chaffeensis exploits host SUMOylation pathways to mediate effector-host interactions and promote intracellular survival. Infection and immunity. 2014;82(10):4154–68. Epub 2014/07/23. doi: 10.1128/IAI.01984-14 25047847; PubMed Central PMCID: PMCPMC4187855.
53. Dedonder SE, Cheng C, Willard LH, Boyle DL, Ganta RR, Transmission electron microscopy reveals distinct macrophage- and tick cell-specific morphological stages of Ehrlichia chaffeensis. PloS one. 2012;7(5):e36749. Epub 2012/05/23. doi: 10.1371/journal.pone.0036749 22615806; PubMed Central PMCID: PMCPMC3352939.
54. Von Ohlen T, Luce-Fedrow A, Ortega MT, Ganta RR, Chapes SK, Identification of critical host mitochondrion-associated genes during Ehrlichia chaffeensis infections. Infection and immunity. 2012;80(10):3576–86. Epub 2012/08/02. doi: 10.1128/IAI.00670-12 22851751; PubMed Central PMCID: PMCPMC3457586.
55. Rikihisa Y, Subversion of RAB5-regulated autophagy by the intracellular pathogen Ehrlichia chaffeensis. Small GTPases. 2017:1–7. Epub 2017/06/27. doi: 10.1080/21541248.2017.1332506 28650718.
56. McNab F, Mayer-Barber K, Sher A, Wack A, O'Garra A, Type I interferons in infectious disease. Nature reviews Immunology. 2015;15(2):87–103. Epub 2015/01/24. doi: 10.1038/nri3787 25614319.
57. Hall JC, Rosen A, Type I interferons: crucial participants in disease amplification in autoimmunity. Nature reviews Rheumatology. 2010;6(1):40–9. Epub 2010/01/05. doi: 10.1038/nrrheum.2009.237 20046205; PubMed Central PMCID: PMCPMC3622245.
58. Crouse J, Kalinke U, Oxenius A, Regulation of antiviral T cell responses by type I interferons. Nature reviews Immunology. 2015;15(4):231–42. Epub 2015/03/21. doi: 10.1038/nri3806 25790790.
59. Ivashkiv LB, Donlin LT, Regulation of type I interferon responses. Nature reviews Immunology. 2014;14(1):36–49. Epub 2013/12/24. doi: 10.1038/nri3581 24362405; PubMed Central PMCID: PMCPMC4084561.
60. Sehdev AE, Dumler JS, Hepatic pathology in human monocytic ehrlichiosis. Ehrlichia chaffeensis infection. American journal of clinical pathology. 2003;119(6):859–65. Epub 2003/06/24. doi: 10.1309/F7EA-B5P7-3217-16LJ 12817434.
61. Amer AO, The many uses of autophagosomes. Autophagy. 2013;9(5):633–4. Epub 2013/03/20. doi: 10.4161/auto.24146 23507956; PubMed Central PMCID: PMCPMC3669174.
62. Amer AO, Swanson MS, Autophagy is an immediate macrophage response to Legionella pneumophila. Cellular microbiology. 2005;7(6):765–78. Epub 2005/05/13. doi: 10.1111/j.1462-5822.2005.00509.x 15888080; PubMed Central PMCID: PMCPMC1584279.
63. Birmingham CL, Brumell JH, Autophagy recognizes intracellular Salmonella enterica serovar Typhimurium in damaged vacuoles. Autophagy. 2006;2(3):156–8. Epub 2006/07/29. 16874057.
64. von Muhlinen N, Thurston T, Ryzhakov G, Bloor S, Randow F, NDP52, a novel autophagy receptor for ubiquitin-decorated cytosolic bacteria. Autophagy. 2010;6(2):288–9. Epub 2010/01/28. 20104023.
65. Liu Y, Zhang Z, Jiang Y, Zhang L, Popov VL, Zhang J, et al. Obligate intracellular bacterium Ehrlichia inhibiting mitochondrial activity. Microbes and infection. 2011;13(3):232–8. Epub 2010/11/13. doi: 10.1016/j.micinf.2010.10.021 21070861; PubMed Central PMCID: PMCPMC3031727.
66. Sasai M, Linehan MM, Iwasaki A, Bifurcation of Toll-like receptor 9 signaling by adaptor protein 3. Science (New York, NY). 2010;329(5998):1530–4. Epub 2010/09/18. doi: 10.1126/science.1187029 20847273; PubMed Central PMCID: PMCPMC3063333.
67. Garcia-Martinez I, Santoro N, Chen Y, Hoque R, Ouyang X, Caprio S, et al. Hepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9. The Journal of clinical investigation. 2016;126(3):859–64. Epub 2016/01/26. doi: 10.1172/JCI83885 26808498; PubMed Central PMCID: PMCPMC4767345.
68. Cocita C, Guiton R, Bessou G, Chasson L, Boyron M, Crozat K, et al. Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus. PLoS pathogens. 2015;11(5):e1004897. Epub 2015/05/09. doi: 10.1371/journal.ppat.1004897 25954804; PubMed Central PMCID: PMCPMC4425567.
69. Delale T, Paquin A, Asselin-Paturel C, Dalod M, Brizard G, Bates EE, et al. MyD88-dependent and -independent murine cytomegalovirus sensing for IFN-alpha release and initiation of immune responses in vivo. Journal of immunology (Baltimore, Md: 1950). 2005;175(10):6723–32. Epub 2005/11/08. 16272328.
70. Liu H, Bao W, Lin M, Niu H, Rikihisa Y, Ehrlichia type IV secretion effector ECH0825 is translocated to mitochondria and curbs ROS and apoptosis by upregulating host MnSOD. Cellular microbiology. 2012;14(7):1037–50. Epub 2012/02/22. doi: 10.1111/j.1462-5822.2012.01775.x 22348527; PubMed Central PMCID: PMCPMC3371182.
71. Dunphy PS, Luo T, McBride JW, Ehrlichia moonlighting effectors and interkingdom interactions with the mononuclear phagocyte. Microbes and infection. 2013;15(14–15):1005–16. doi: 10.1016/j.micinf.2013.09.011 24141087; PubMed Central PMCID: PMC3886233.
72. Uhl M, Kepp O, Jusforgues-Saklani H, Vicencio JM, Kroemer G, Albert ML, Autophagy within the antigen donor cell facilitates efficient antigen cross-priming of virus-specific CD8+ T cells. Cell death and differentiation. 2009;16(7):991–1005. Epub 2009/02/21. doi: 10.1038/cdd.2009.8 19229247.
73. Aneja RK, Tsung A, Sjodin H, Gefter JV, Delude RL, Billiar TR, et al. Preconditioning with high mobility group box 1 (HMGB1) induces lipopolysaccharide (LPS) tolerance. Journal of leukocyte biology. 2008;84(5):1326–34. Epub 2008/08/09. doi: 10.1189/jlb.0108030 18687905; PubMed Central PMCID: PMCPMC2567896.
74. Fang R, Ismail N, Soong L, Popov VL, Whitworth T, Bouyer DH, et al. Differential interaction of dendritic cells with Rickettsia conorii: impact on host susceptibility to murine spotted fever rickettsiosis. Infection and immunity. 2007;75(6):3112–23. Epub 2007/04/04. doi: 10.1128/IAI.00007-07 17403875; PubMed Central PMCID: PMCPMC1932850.
75. Bjorkoy G, Lamark T, Pankiv S, Overvatn A, Brech A, Johansen T, Monitoring autophagic degradation of p62/SQSTM1. Methods in enzymology. 2009;452:181–97. Epub 2009/02/10. doi: 10.1016/S0076-6879(08)03612-4 19200883.
76. Doyle CK, Labruna MB, Breitschwerdt EB, Tang YW, Corstvet RE, Hegarty BC, et al. Detection of medically important Ehrlichia by quantitative multicolor TaqMan real-time polymerase chain reaction of the dsb gene. J Mol Diagn. 2005;7(4):504–10. Epub 2005/10/21. doi: 10.1016/S1525-1578(10)60581-8 16237220; PubMed Central PMCID: PMCPMC1888493.
77. Sumner JW, Storch GA, Buller RS, Liddell AM, Stockham SL, Rikihisa Y, et al. PCR amplification and phylogenetic analysis of groESL operon sequences from Ehrlichia ewingii and Ehrlichia muris. Journal of clinical microbiology. 2000;38(7):2746–9. Epub 2000/07/06. 10878077; PubMed Central PMCID: PMCPMC87017.
78. Rikihisa Y, Kawahara M, Wen B, Kociba G, Fuerst P, Kawamori F, et al. Western immunoblot analysis of Haemobartonella muris and comparison of 16S rRNA gene sequences of H. muris, H. felis, and Eperythrozoon suis. Journal of clinical microbiology. 1997;35(4):823–9. Epub 1997/04/01. 9157135; PubMed Central PMCID: PMCPMC229683.