Infection homeostasis: implications for therapeutic and immune programming of metabolism in controlling infection

Medical Microbiology and Immunology

Volumn 204, Issue 3, 2015, Pages 395-407

  Kotzamanis, Konstantinos ^a   Angulo, Ana ^b   Ghazal, Peter ^a,c  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b UNIVERSITY OF BARCELONA   (Spain)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

CMV; Fatty acid synthesis; Glycolysis; Infection; Inflammation; Metabolism

Indexed keywords

CHOLESTEROL; GLUTAMINE; LONG CHAIN FATTY ACID; MEVALONIC ACID; PROSTANOID; STEROL;

AMINO ACID METABOLISM; CELL ACTIVATION; CELL STIMULATION; CHOLESTEROL SYNTHESIS; CYTOMEGALOVIRUS INFECTION; DENDRITIC CELL; FATTY ACID SYNTHESIS; GLYCOLYSIS; HOMEOSTASIS; HUMAN; IMMUNOREGULATION; INFECTION CONTROL; INFLAMMATION; LIPID ANALYSIS; LIPID METABOLISM; MACROPHAGE ACTIVATION; METABOLISM; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; VIROGENESIS; ANIMAL; CARBOHYDRATE METABOLISM; DRUG EFFECTS; ENERGY METABOLISM; HOST PATHOGEN INTERACTION; IMMUNOLOGY; IMMUNOMODULATION; INFECTION;

ANIMALS; CARBOHYDRATE METABOLISM; ENERGY METABOLISM; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNOMODULATION; INFECTION; LIPID METABOLISM;

EID: 84929958508     PISSN: 03008584     EISSN: 14321831     Source Type: Journal    
DOI: 10.1007/s00430-015-0402-5     Document Type: Review

References (109)

1. Ghazal P, González Armas JC, García-Ramírez JJ et al (2000) Viruses: hostages to the cell. Virology 275:233–237. doi:10.1006/viro.2000.0553
2. Redpath S, Angulo A, Gascoigne NR, Ghazal P (2001) Immune checkpoints in viral latency. Annu Rev Microbiol 55:531–560. doi:10.1146/annurev.micro.55.1.531
3. Ghazal P, García-Ramírez J, González-Armas JC et al (2000) Principles of homeostasis in governing virus activation and latency. Immunol Res 21:219–223. doi:10.1385/IR:21:2-3:219
4. Holthuis JCM, Menon AK (2014) Lipid landscapes and pipelines in membrane homeostasis. Nature 510:48–57. doi:10.1038/nature13474
5. Jeon T, Il Osborne TF (2012) SREBPs: metabolic integrators in physiology and metabolism. Trends Endocrinol Metab 23:65–72. doi:10.1016/j.tem.2011.10.004
6. Palazon A, Goldrath AW, Nizet V, Johnson RS (2014) Review HIF transcription factors, inflammation, and immunity. Immunity 41:518–528. doi:10.1016/j.immuni.2014.09.008
7. McNelis J, Olefsky J (2014) Macrophages, immunity, and metabolic disease. Immunity 41:36–48. doi:10.1016/j.immuni.2014.05.010
8. Maceyka M, Spiegel S (2014) Sphingolipid metabolites in inflammatory disease. Nature 510:58–67. doi:10.1038/nature13475
9. Everts B, Pearce EJ (2014) Metabolic control of dendritic cell activation and function: recent advances and clinical implications. Front Immunol 5:1–7. doi:10.3389/fimmu.2014.00203
10. Cyster JG, Dang EV, Reboldi A, Yi T (2014) 25-Hydroxycholesterols in innate and adaptive immunity. Nat Rev Immunol 14:731–743. doi:10.1038/nri3755
11. Koyuncu E, Purdy JG, Rabinowitz JD, Shenk T (2013) Saturated very long chain fatty acids are required for the production of infectious human cytomegalovirus progeny. PLoS Pathog 9:e1003333. doi:10.1371/journal.ppat.1003333
12. Moser TS, Schieffer D, Cherry S (2012) AMP-activated kinase restricts Rift Valley fever virus infection by inhibiting fatty acid synthesis. PLoS Pathog 8:e1002661. doi:10.1371/journal.ppat.1002661
13. Zheng Y-H, Plemenitas A, Fielding CJ, Peterlin BM (2003) Nef increases the synthesis of and transports cholesterol to lipid rafts and HIV-1 progeny virions. Proc Natl Acad Sci USA 100:8460–8465. doi:10.1073/pnas.1437453100
14. Vastag L, Koyuncu E, Grady SL et al (2011) Divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism. PLoS Pathog 7:e1002124. doi:10.1371/journal.ppat.1002124
15. Blanc M, Hsieh WY, Robertson KA et al (2011) Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. PLoS Biol 9:e1000598. doi:10.1371/journal.pbio.1000598
16. Blanc M, Hsieh WY, Robertson KA et al (2013) The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Immunity 38:106–118. doi:10.1016/j.immuni.2012.11.004
17. Deberardinis RJ, Sayed N, Ditsworth D, Thompson CB (2008) Brick by brick: metabolism and tumor cell growth. Curr Opin Genet Dev 18:54–61. doi:10.1016/j.gde.2008.02.003
18. Vander Heiden MG, Locasale JW, Swanson KD et al (2010) Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 329:1492–1499. doi:10.1126/science.1188015
19. DeBerardinis RJ, Mancuso A, Daikhin E et al (2007) Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA 104:19345–19350. doi:10.1073/pnas.0709747104
20. Kim J, Dang CV (2006) Cancer’s molecular sweet tooth and the Warburg effect. Cancer Res 66:8927–8930. doi:10.1158/0008-5472.CAN-06-1501
21. Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033. doi:10.1126/science.1160809
22. Menendez JA, Lupu R (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 7:763–777. doi:10.1038/nrc2222
23. Swinnen JV, Brusselmans K, Verhoeven G (2006) Increased lipogenesis in cancer cells: new players, novel targets. Curr Opin Clin Nutr Metab Care 9:358–365. doi:10.1097/01.mco.0000232894.28674.30
24. Munger J, Bajad SU, Coller HA et al (2006) Dynamics of the cellular metabolome during human cytomegalovirus infection. PLoS Pathog 2:e132. doi:10.1371/journal.ppat.0020132
25. Munger J, Bennett BD, Parikh A et al (2008) Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy. Nat Biotechnol 26:1179–1186. doi:10.1038/nbt.1500
26. Yu Y, Clippinger AJ, Alwine JC (2011) Viral effects on metabolism: changes in glucose and glutamine utilization during human cytomegalovirus infection. Trends Microbiol 19:360–367. doi:10.1016/j.tim.2011.04.002
27. McArdle J, Moorman NJ, Munger J (2012) HCMV targets the metabolic stress response through activation of AMPK whose activity is important for viral replication. PLoS Pathog 8:e1002502. doi:10.1371/journal.ppat.1002502
28. Yu Y, Pierciey FJ, Maguire TG, Alwine JC (2013) PKR-like endoplasmic reticulum kinase is necessary for lipogenic activation during HCMV infection. PLoS Pathog 9(9):e1003266. doi:10.1371/journal.ppat.1003266
29. Yu Y, Maguire TG, Alwine JC (2012) Human cytomegalovirus infection induces adipocyte-like lipogenesis through activation of sterol regulatory element binding protein 1. J Virol 86:2942–2949. doi:10.1128/JVI.06467-11
30. Yu Y, Maguire TG, Alwine JC (2014) ChREBP, a glucose-responsive transcriptional factor, enhances glucose metabolism to support biosynthesis in human cytomegalovirus-infected cells. Proc Natl Acad Sci USA 111:1951–1956. doi:10.1073/pnas.1310779111
31. Yu Y, Maguire TG, Alwine JC (2011) Human cytomegalovirus activates glucose transporter 4 expression to increase glucose uptake during infection. J Virol 85:1573–1580. doi:10.1128/JVI.01967-10
32. Chambers JW, Maguire TG, Alwine JC (2010) Glutamine metabolism is essential for human cytomegalovirus infection. J Virol 84:1867–1873. doi:10.1128/JVI.02123-09
33. Seo J-Y, Cresswell P (2013) Viperin regulates cellular lipid metabolism during human cytomegalovirus infection. PLoS Pathog 9:e1003497. doi:10.1371/journal.ppat.1003497
34. Seo J-Y, Yaneva R, Cresswell P (2011) Viperin: a multifunctional, interferon-inducible protein that regulates virus replication. Cell Host Microbe 10:534–539. doi:10.1016/j.chom.2011.11.004
35. Seo J-Y, Yaneva R, Hinson ER, Cresswell P (2011) Human cytomegalovirus directly induces the antiviral protein viperin to enhance infectivity. Science 332:1093–1097. doi:10.1126/science.1202007
36. Spencer CM, Schafer XL, Moorman NJ, Munger J (2011) Human cytomegalovirus induces the activity and expression of acetyl-coenzyme A carboxylase, a fatty acid biosynthetic enzyme whose inhibition attenuates viral replication. J Virol 85:5814–5824. doi:10.1128/JVI.02630-10
37. Radsak KD, Weder D (1981) Effect of 2-deoxy-d-glucose on cytomegalovirus-induced DNA synthesis in human fibroblasts. J Gen Virol 57:33–42
38. Ghesquière B, Wong BW, Kuchnio A, Carmeliet P (2014) Metabolism of stromal and immune cells in health and disease. Nature 511:167–176. doi:10.1038/nature13312
39. Pearce EL (2010) Metabolism in T cell activation and differentiation. Curr Opin Immunol 22:314–320. doi:10.1016/j.coi.2010.01.018
40. Chang C-H, Curtis JD, Maggi LB et al (2013) Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 153:1239–1251. doi:10.1016/j.cell.2013.05.016
41. Pearce EL, Poffenberger MC, Chang C-H, Jones RG (2013) Fueling immunity: insights into metabolism and lymphocyte function. Science 342:1242454. doi:10.1126/science.1242454
42. Pearce EL, Pearce EJ (2013) Metabolic pathways in immune cell activation and quiescence. Immunity 38:633–643. doi:10.1016/j.immuni.2013.04.005
43. Rodríguez-Prados J-C, Través PG, Cuenca J et al (2010) Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation. J Immunol 185:605–614. doi:10.4049/jimmunol.0901698
44. Everts B, Amiel E, van der Windt GJW et al (2012) Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells. Blood 120:1422–1431. doi:10.1182/blood-2012-03-419747
45. West AP, Brodsky IE, Rahner C et al (2011) TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature 472:476–480. doi:10.1038/nature09973
46. Krawczyk CM, Holowka T, Sun J et al (2010) Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood 115:4742–4749. doi:10.1182/blood-2009-10-249540
47. Everts B, Amiel E, Huang SC-C et al (2014) TLR-driven early glycolytic reprogramming via the kinases TBK1-IKK[epsiv] supports the anabolic demands of dendritic cell activation. Nat Immunol 15:323–332. doi:10.1038/ni.2833
48. Galván-Peña S, O’Neill LAJ (2014) Metabolic reprogramming in macrophage polarization. Front Immunol 5:1–6. doi:10.3389/fimmu.2014.00420
49. McGettrick AF, O’Neill LAJ (2013) How metabolism generates signals during innate immunity and inflammation. J Biol Chem 288:22893–22898. doi:10.1074/jbc.R113.486464
50. Freemerman AJ, Johnson AR, Sacks GN et al (2014) Metabolic reprogramming of macrophages: glucose transporter 1 (GLUT1)-mediated glucose metabolism drives a proinflammatory phenotype. J Biol Chem 289:7884–7896. doi:10.1074/jbc.M113.522037
51. Hannun YA, Obeid LM (2008) Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol 9:139–150. doi:10.1038/nrm2329
52. Angulo A, Suto C, Boehm MF et al (1995) Retinoid activation of retinoic acid receptors but not of retinoid X receptors promotes cellular differentiation and replication of human cytomegalovirus in embryonal cells. J Virol 69:3831–3837
53. Ghazal P, DeMattei C, Giulietti E et al (1992) Retinoic acid receptors initiate induction of the cytomegalovirus enhancer in embryonal cells. Proc Natl Acad Sci USA 89:7630–7634. doi:10.1073/pnas.89.16.7630
54. Angulo A, Chandraratna RA, LeBlanc JF, Ghazal P (1998) Ligand induction of retinoic acid receptors alters an acute infection by murine cytomegalovirus. J Virol 72:4589–4600
55. Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509. doi:10.1371/journal.pone.0020510
56. Jakobsson A, Westerberg R, Jacobsson A (2006) Fatty acid elongases in mammals: their regulation and roles in metabolism. Prog Lipid Res 45:237–249. doi:10.1016/j.plipres.2006.01.004
57. Liu STH, Sharon-Friling R, Ivanova P et al (2011) Synaptic vesicle-like lipidome of human cytomegalovirus virions reveals a role for SNARE machinery in virion egress. Proc Natl Acad Sci USA 108:12869–12874. doi:10.1073/pnas.1109796108
58. Alwine JC (2012) The human cytomegalovirus assembly compartment: a masterpiece of viral manipulation of cellular processes that facilitates assembly and egress. PLoS Pathog 8:e1002878. doi:10.1371/journal.ppat.1002878
59. Das S, Pellett PE (2007) Members of the HCMV US12 family of predicted heptaspanning membrane proteins have unique intracellular distributions, including association with the cytoplasmic virion assembly complex. Virology 361:263–273. doi:10.1016/j.virol.2006.11.019
60. Das S, Pellett PE (2011) Spatial relationships between markers for secretory and endosomal machinery in human cytomegalovirus-infected cells versus those in uninfected cells. J Virol 85:5864–5879. doi:10.1128/JVI.00155-11
61. Das S, Vasanji A, Pellett PE (2007) Three-dimensional structure of the human cytomegalovirus cytoplasmic virion assembly complex includes a reoriented secretory apparatus. J Virol 81:11861–11869. doi:10.1128/JVI.01077-07
62. Zelcer N, Tontonoz P (2006) Liver X receptors as integrators of metabolic and inflammatory signaling. J Clin Invest 116:607–614. doi:10.1172/JCI27883
63. Castrillo A, Joseph SB, Vaidya SA et al (2003) Crosstalk between LXR and Toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism. Mol Cell 12:805–816. doi:10.1016/S1097-2765(03)00384-8
64. Wang S, Wu D, Lamon-Fava S et al (2009) In vitro fatty acid enrichment of macrophages alters inflammatory response and net cholesterol accumulation. Br J Nutr 102:497–501. doi:10.1017/S0007114509231758
65. Ecker J, Liebisch G, Englmaier M et al (2010) Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes. Proc Natl Acad Sci USA 107:7817–7822. doi:10.1073/pnas.0912059107
66. Shibata N, Carlin AF, Spann NJ et al (2013) 25-Hydroxycholesterol activates the integrated stress response to reprogram transcription and translation in macrophages. J Biol Chem 288:35812–35823. doi:10.1074/jbc.M113.519637
67. Browne EP, Wing B, Coleman D, Shenk T (2001) Altered cellular mRNA levels in human cytomegalovirus-infected fibroblasts: viral block to the accumulation of antiviral mRNAs. J Virol 75:12319–12330. doi:10.1128/JVI.75.24.12319-12330.2001
68. Simmen KA, Singh J, Luukkonen BG et al (2001) Global modulation of cellular transcription by human cytomegalovirus is initiated by viral glycoprotein B. Proc Natl Acad Sci USA 98:7140–7145. doi:10.1073/pnas.121177598
69. AbuBakar S, Boldogh I, Albrecht T (1990) Human cytomegalovirus stimulates arachidonic acid metabolism through pathways that are affected by inhibitors of phospholipase A2 and protein kinase C. Biochem Biophys Res Commun 166:953–959. doi:10.1016/0006-291X(90)90903-Z
70. Bos CL, Richel DJ, Ritsema T et al (2004) Prostanoids and prostanoid receptors in signal transduction. Int J Biochem Cell Biol 36:1187–1205. doi:10.1016/j.biocel.2003.08.006
71. Schröer J, Shenk T (2008) Inhibition of cyclooxygenase activity blocks cell-to-cell spread of human cytomegalovirus. Proc Natl Acad Sci USA 105:19468–19473. doi:10.1073/pnas.0810740105
72. Zhu H, Cong J-P, Yu D et al (2002) Inhibition of cyclooxygenase 2 blocks human cytomegalovirus replication. Proc Natl Acad Sci USA 99:3932–3937. doi:10.1073/pnas.052713799
73. Lee KJ, Angulo A, Ghazal P, Janda KD (1999) Soluble-polymer supported synthesis of a prostanoid library: identification of antiviral activity. Org Lett 1:1859–1862
74. Sirois P, Cadieux A, Rola-Pleszczynski M, Bégin R (1982) Perifused alveolar macrophages. A technique to study the effects of toxicants on prostaglandin release. Experientia 38:1125–1127. doi:10.1007/BF01955404
75. Infantino V, Convertini P, Cucci L et al (2011) The mitochondrial citrate carrier: a new player in inflammation. Biochem J 438:433–436. doi:10.1042/BJ20111275
76. Dennis EA, Deems RA, Harkewicz R et al (2010) A mouse macrophage lipidome. J Biol Chem 285:39976–39985. doi:10.1074/jbc.M110.182915
77. Biswas SK, Mantovani A (2012) Orchestration of metabolism by macrophages. Cell Metab 15:432–437. doi:10.1016/j.cmet.2011.11.013
78. Hirata T, Narumiya S (2012) Prostanoids as regulators of innate and adaptive immunity. Adv Immunol 116:143–174. doi:10.1016/B978-0-12-394300-2.00005-3
79. Martinez FO, Gordon S, Locati M, Mantovani A (2006) Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol 177:7303–7311. doi:10.1016/S1077-9108(08)70760-6
80. Mosca M, Polentarutti N, Mangano G et al (2007) Regulation of the microsomal prostaglandin E synthase-1 in polarized mononuclear phagocytes and its constitutive expression in neutrophils. J Leukoc Biol 82:320–326. doi:10.1189/jlb.0906576
81. Diaz-Munoz MD, Osma-Garcia IC, Fresno M, Iniguez MA (2012) Involvement of PGE2 and the cAMP signalling pathway in the up-regulation of COX-2 and mPGES-1 expression in LPS-activated macrophages. Biochem J 443:451–461. doi:10.1042/BJ20111052
82. Nataraj C, Thomas DW, Tilley SL et al (2001) Receptors for prostaglandin E2 that regulate cellular immune responses in the mouse. J Clin Invest 108:1229–1235. doi:10.1172/JCI13640 (Introduction)
83. Vassiliou E, Jing H, Ganea D (2003) Prostaglandin E2 inhibits TNF production in murine bone marrow-derived dendritic cells. Cell Immunol 223:120–132. doi:10.1016/S0008-8749(03)00158-8
84. Harizi H, Grosset C, Gualde N (2003) Prostaglandin E2 modulates dendritic cell function via EP2 and EP4 receptor subtypes. J Leukoc Biol 73:756–763. doi:10.1189/jlb.1002483
85. Yao C, Sakata D, Esaki Y et al (2009) Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion. Nat Med 15:633–640. doi:10.1038/nm.1968
86. Nokta MA, Hassan MI, Loesch K, Pollard RB (1996) Human cytomegalovirus-induced immunosuppression relationship to prostaglandin E2 in human monocytes. J Clin Invest 97:2635–2641
87. Ogawa S, Lozach J, Benner C et al (2005) Molecular determinants of crosstalk between nuclear receptors and toll-like receptors. Cell 122:707–721. doi:10.1016/j.cell.2005.06.029
88. Lees RS, Fiser RH, Beisel WR, Bartelloni PJ (1972) Effects of an experimental viral infection on plasma lipid and lipoprotein metabolism. Metabolism 21:825–833
89. Sole A (1956) Serum cholesterol in measles. Arch Kinderheilkd 152:127–135
90. Viikari J, Ruuskanen O, Salmi T, Halonen P (1979) Effect of measles and measles vaccine on serum-cholesterol. Lancet 1:326. doi:10.1016/S0140-6736(79)90738-4
91. Isaacs A, Lindenmann J (1957) Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci 147:258–267
92. Cantell K, Ehnholm C, Mattila K, Kostiainen E (1980) Interferon and high-density lipoproteins. N Engl J Med 302:1032–1033. doi:10.1056/NEJM198005013021817
93. Rosenzweig IB, Wiebe DA, Borden EC et al (1987) Plasma lipoprotein changes in humans induced by beta-interferon. Atherosclerosis 67:261–267
94. Schectman G, Kaul S, Mueller RA et al (1992) The effect of interferon on the metabolism of LDLs. Arterioscler Thromb 12:1053–1062. doi:10.1161/01.ATV.12.9.1053
95. Borden EC, Rinehart JJ, Storer BE et al (1990) Biological and clinical effects of interferon-beta ser at two doses. J Interferon Res 10:559–570
96. Shope RE (1930) Variations in the plasma cholesterol and cholesterol ester content in hog cholera. J Exp Med 51:179–187
97. Iqbal M, Grand NG (1973) Biochemical events in murine cytomegalovirus-infected mouse liver. Proc Soc Exp Biol Med 142:567–571
98. Ponroy N, Taveira A, Mueller NJ, Millard AL (2015) Statins demonstrate a broad anti-cytomegalovirus activity in vitro in ganciclovir-susceptible and resistant strains. J Med Virol. doi:10.1002/jmv.23998
99. Potena L, Frascaroli G, Grigioni F et al (2004) Hydroxymethyl-glutaryl coenzyme A reductase inhibition limits cytomegalovirus infection in human endothelial cells. Circulation 109:532–536. doi:10.1161/01.CIR.0000109485.79183.81
100. Murayama T, Bi C, Li Y et al (2011) Inhibitory effects of statins on cytomegalovirus production in human cells: comprehensive analysis of gene expression profiles. J Exp Clin Med 3:40–45. doi:10.1016/j.jecm.2010.12.009
101. Watterson S, Guerriero ML, Blanc M et al (2013) A model of flux regulation in the cholesterol biosynthesis pathway: immune mediated graduated flux reduction versus statin-like led stepped flux reduction. Biochimie 95:613–621. doi:10.1016/j.biochi.2012.05.024
102. Gudleski-O’Regan N, Greco TM, Cristea IM, Shenk T (2012) Increased expression of LDL receptor-related protein 1 during human cytomegalovirus infection reduces virion cholesterol and infectivity. Cell Host Microbe 12:86–96. doi:10.1016/j.chom.2012.05.012
103. Liu S-Y, Aliyari R, Chikere K et al (2012) Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol. Immunity 38:92–105. doi:10.1016/j.immuni.2012.11.005
104. Preuss I, Ludwig M-G, Baumgarten B et al (2014) Transcriptional regulation and functional characterization of the oxysterol/EBI2 system in primary human macrophages. Biochem Biophys Res Commun 446:663–668. doi:10.1016/j.bbrc.2014.01.069
105. Lu H, Talbot S, Robertson KA et al (2015) Rapid proteasomal elimination of 3-hydroxy-3-methylglutaryl-coenzyme A reductase by interferon-gamma in primary macrophages requires endogenous 25-hydroxycholesterol synthesis. Steroids. doi:10.1016/j.steroids.2015.02.022
106. Reboldi A, Dang EV, McDonald JG et al (2014) 25-Hydroxycholesterol suppresses interleukin-1-driven inflammation downstream of type I interferon. Science 345:679–684. doi:10.1126/science.1254790
107. Ghazal P, Watterson S, Robertson K, Kluth DC (2011) The in silico macrophage: toward a better understanding of inflammatory disease. Genome Med 3:1–7. doi:10.1186/gm218
108. Burrack KS, Morrison TE (2014) The role of myeloid cell activation and arginine metabolism in the pathogenesis of virus-induced diseases. Front Immunol 5:1–12. doi:10.3389/fimmu.2014.00428
109. Heseler K, Schmidt SK, Spekker K et al (2013) Cytomegalovirus impairs the induction of indoleamine 2,3-dioxygenase mediated antimicrobial and immunoregulatory effects in human fibroblasts. PLoS ONE 8:1–7. doi:10.1371/journal.pone.0064442