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Annual Review of Pathology: Mechanisms of Disease

Volume 14, 2019

Innate Immune Signaling in Nonalcoholic Fatty Liver Disease and Cardiovascular Diseases

Abstract

The physiological significance of innate immune signaling lies primarily in its role in host defense against invading pathogens. It is becoming increasingly clear that innate immune signaling also modulates the development of metabolic diseases, especially nonalcoholic fatty liver disease and cardiovascular diseases, which are characterized by chronic, low-grade inflammation due to a disarrangement of innate immune signaling. Notably, recent studies indicate that in addition to regulating canonical innate immune-mediated inflammatory responses (or immune-dependent signaling-induced responses), molecules of the innate immune system regulate pathophysiological responses in multiple organs during metabolic disturbances (termed immune-independent signaling-induced responses), including the disruption of metabolic homeostasis, tissue repair, and cell survival. In addition, emerging evidence from the study of immunometabolism indicates that the systemic metabolic status may have profound effects on cellular immune function and phenotypes through the alteration of cell-intrinsic metabolism. We summarize how the innate immune system interacts with metabolic disturbances to trigger immune-dependent and immune-independent pathogenesis in the context of nonalcoholic fatty liver disease, as representative of metabolic diseases, and cardiovascular diseases.

Keyword(s): cardiovascular disease, CVD, immunometabolism, innate immunity, metabolic disease, NAFLD, nonalcoholic fatty liver disease
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/content/journals/10.1146/annurev-pathmechdis-012418-013003
2019-01-24
2024-04-19
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Literature Cited

  1. 1.  Newton K, Dixit VM 2012. Signaling in innate immunity and inflammation. Cold Spring Harb. Perspect. Biol. 4:a006049
     [Google Scholar]
  2. 2.  Epelman S, Liu PP, Mann DL 2015. Role of innate and adaptive immune mechanisms in cardiac injury and repair. Nat. Rev. Immunol. 15:117–29
     [Google Scholar]
  3. 3.  Schuster S, Cabrera D, Arrese M, Feldstein AE 2018. Triggering and resolution of inflammation in NASH. Nat. Rev. Gastroenterol. Hepatol. 15:349–64
     [Google Scholar]
  4. 4.  Nishida K, Otsu K 2017. Inflammation and metabolic cardiomyopathy. Cardiovasc. Res. 113:389–98
     [Google Scholar]
  5. 5.  O'Neill LA, Kishton RJ, Rathmell J 2016. A guide to immunometabolism for immunologists. Nat. Rev. Immunol. 16:553–65
     [Google Scholar]
  6. 6.  Netea MG, Joosten LA, Latz E, Mills KH, Natoli G et al. 2016. Trained immunity: a program of innate immune memory in health and disease. Science 352:aaf1098
     [Google Scholar]
  7. 7.  Friedman SL, Ratziu V, Harrison SA, Abdelmalek MF, Aithal GP et al. 2018. A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis. Hepatology 67:1754–67
     [Google Scholar]
  8. 8.  Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH et al. 2017. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377:1119–31
     [Google Scholar]
  9. 9.  Brubaker SW, Bonham KS, Zanoni I, Kagan JC 2015. Innate immune pattern recognition: a cell biological perspective. Annu. Rev. Immunol. 33:257–90
     [Google Scholar]
  10. 10.  Guebre-Xabier M, Yang S, Lin HZ, Schwenk R, Krzych U, Diehl AM 2000. Altered hepatic lymphocyte subpopulations in obesity-related murine fatty livers: potential mechanism for sensitization to liver damage. Hepatology 31:633–40
     [Google Scholar]
  11. 11.  Bekkering S, Quintin J, Joosten LA, van der Meer JW, Netea MG, Riksen NP 2014. Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell formation via epigenetic reprogramming of monocytes. Arterioscler. Thromb. Vasc. Biol. 34:1731–38
     [Google Scholar]
  12. 12.  Nguyen KD, Qiu Y, Cui X, Goh YP, Mwangi J et al. 2011. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature 480:104–8
     [Google Scholar]
  13. 13.  Hulsmans M, Clauss S, Xiao L, Aguirre AD, King KR et al. 2017. Macrophages facilitate electrical conduction in the heart. Cell 169:510–22
     [Google Scholar]
  14. 14.  Arrese M, Cabrera D, Kalergis AM, Feldstein AE 2016. Innate immunity and inflammation in NAFLD/NASH. Dig. Dis. Sci. 61:1294–303
     [Google Scholar]
  15. 15.  Zhao GN, Zhang P, Gong J, Zhang XJ, Wang PX et al. 2017. Tmbim1 is a multivesicular body regulator that protects against non-alcoholic fatty liver disease in mice and monkeys by targeting the lysosomal degradation of Tlr4. Nat. Med. 23:742–52
     [Google Scholar]
  16. 16.  Li L, Chen L, Hu L, Liu Y, Sun HY et al. 2011. Nuclear factor high-mobility group box1 mediating the activation of Toll-like receptor 4 signaling in hepatocytes in the early stage of nonalcoholic fatty liver disease in mice. Hepatology 54:1620–30
     [Google Scholar]
  17. 17.  Das S, Alhasson F, Dattaroy D, Pourhoseini S, Seth RK et al. 2015. NADPH oxidase–derived peroxynitrite drives inflammation in mice and human nonalcoholic steatohepatitis via TLR4-lipid raft recruitment. Am. J. Pathol. 185:1944–57
     [Google Scholar]
  18. 18.  Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS 2006. TLR4 links innate immunity and fatty acid–induced insulin resistance. J. Clin. Investig. 116:3015–25
     [Google Scholar]
  19. 19.  Spruss A, Kanuri G, Wagnerberger S, Haub S, Bischoff SC, Bergheim I 2009. Toll-like receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice. Hepatology 50:1094–104
     [Google Scholar]
  20. 20.  Rivera CA, Adegboyega P, van Rooijen N, Tagalicud A, Allman M, Wallace M 2007. Toll-like receptor-4 signaling and Kupffer cells play pivotal roles in the pathogenesis of non-alcoholic steatohepatitis. J. Hepatol. 47:571–79
     [Google Scholar]
  21. 21.  De Minicis S, Seki E, Paik YH, Osterreicher CH, Kodama Y et al. 2010. Role and cellular source of nicotinamide adenine dinucleotide phosphate oxidase in hepatic fibrosis. Hepatology 52:1420–30
     [Google Scholar]
  22. 22.  Brun P, Castagliuolo I, Di Leo V, Buda A, Pinzani M et al. 2007. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am. J. Physiol. Gastrointest. Liver Physiol. 292:G518–25
     [Google Scholar]
  23. 23.  Rivera CA, Gaskin L, Allman M, Pang J, Brady K et al. 2010. Toll-like receptor-2 deficiency enhances non-alcoholic steatohepatitis. BMC Gastroenterol 10:52
     [Google Scholar]
  24. 24.  Miura K, Yang L, van Rooijen N, Brenner DA, Ohnishi H, Seki E 2013. Toll-like receptor 2 and palmitic acid cooperatively contribute to the development of nonalcoholic steatohepatitis through inflammasome activation in mice. Hepatology 57:577–89
     [Google Scholar]
  25. 25.  Etienne-Mesmin L, Vijay-Kumar M, Gewirtz AT, Chassaing B 2016. Hepatocyte Toll-like receptor 5 promotes bacterial clearance and protects mice against high-fat diet-induced liver disease. Cell. Mol. Gastroenterol. Hepatol. 2:584–604
     [Google Scholar]
  26. 26.  Garcia-Martinez I, Santoro N, Chen Y, Hoque R, Ouyang X et al. 2016. Hepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9. J. Clin. Investig. 126:859–64
     [Google Scholar]
  27. 27.  Scott MJ, Chen C, Sun Q, Billiar TR 2010. Hepatocytes express functional NOD1 and NOD2 receptors: a role for NOD1 in hepatocyte CC and CXC chemokine production. J. Hepatol. 53:693–701
     [Google Scholar]
  28. 28.  Zhang Y, Zhang XJ, Wang PX, Zhang P, Li H 2017. Reprogramming Innate immune signaling in cardiometabolic disease. Hypertension 69:747–60
     [Google Scholar]
  29. 29.  Takeuchi M, Takino J, Sakasai-Sakai A, Takata T, Ueda T et al. 2014. Involvement of the TAGE–RAGE system in non-alcoholic steatohepatitis: novel treatment strategies. World J. Hepatol. 6:880–93
     [Google Scholar]
  30. 30.  Del Campo JA, Gallego P, Grande L 2018. Role of inflammatory response in liver diseases: therapeutic strategies. World J. Hepatol. 10:1–7
     [Google Scholar]
  31. 31.  Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ et al. 2012. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482:179–85
     [Google Scholar]
  32. 32.  Mridha AR, Wree A, Robertson AAB, Yeh MM, Johnson CD et al. 2017. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice. J. Hepatol. 66:1037–46
     [Google Scholar]
  33. 33.  Shen L, Yang Y, Ou T, Key CC, Tong SH et al. 2017. Dietary PUFAs attenuate NLRP3 inflammasome activation via enhancing macrophage autophagy. J. Lipid Res. 58:1808–21
     [Google Scholar]
  34. 34.  Xu L, Bai Q, Rodriguez-Agudo D, Hylemon PB, Heuman DM et al. 2010. Regulation of hepatocyte lipid metabolism and inflammatory response by 25-hydroxycholesterol and 25-hydroxycholesterol-3-sulfate. Lipids 45:821–32
     [Google Scholar]
  35. 35.  Xiang M, Wang PX, Wang AB, Zhang XJ, Zhang Y et al. 2016. Targeting hepatic TRAF1–ASK1 signaling to improve inflammation, insulin resistance, and hepatic steatosis. J. Hepatol. 64:1365–77
     [Google Scholar]
  36. 36.  Zhang P, Wang PX, Zhao LP, Zhang X, Ji YX et al. 2017. The deubiquitinating enzyme TNFAIP3 mediates inactivation of hepatic ASK1 and ameliorates nonalcoholic steatohepatitis. Nat. Med. 24:84–94
     [Google Scholar]
  37. 37.  Chen Z, Sheng L, Shen H, Zhao Y, Wang S et al. 2012. Hepatic TRAF2 regulates glucose metabolism through enhancing glucagon responses. Diabetes 61:566–73
     [Google Scholar]
  38. 38.  Wang PX, Zhang XJ, Luo P, Jiang X, Zhang P et al. 2016. Hepatocyte TRAF3 promotes liver steatosis and systemic insulin resistance through targeting TAK1-dependent signalling. Nat. Commun. 7:10592
     [Google Scholar]
  39. 39.  Gao L, Wang PX, Zhang Y, Yu CJ, Ji Y et al. 2016. Tumor necrosis factor receptor–associated factor 5 (Traf5) acts as an essential negative regulator of hepatic steatosis. J. Hepatol. 65:125–36
     [Google Scholar]
  40. 40.  Inokuchi-Shimizu S, Park EJ, Roh YS, Yang L, Zhang B et al. 2014. TAK1-mediated autophagy and fatty acid oxidation prevent hepatosteatosis and tumorigenesis. J. Clin. Investig. 124:3566–78
     [Google Scholar]
  41. 41.  Ji YX, Huang Z, Yang X, Wang X, Zhao LP et al. 2018. The deubiquitinating enzyme cylindromatosis mitigates nonalcoholic steatohepatitis. Nat. Med. 24:213–23
     [Google Scholar]
  42. 42.  Wang XA, Deng S, Jiang D, Zhang R, Zhang S et al. 2013. CARD3 deficiency exacerbates diet-induced obesity, hepatosteatosis, and insulin resistance in male mice. Endocrinology 154:685–97
     [Google Scholar]
  43. 43.  Wang XA, Zhang R, She ZG, Zhang XF, Jiang DS et al. 2014. Interferon regulatory factor 3 constrains IKKβ/NF-κB signaling to alleviate hepatic steatosis and insulin resistance. Hepatology 59:870–85
     [Google Scholar]
  44. 44.  Dalmas E, Toubal A, Alzaid F, Blazek K, Eames HL et al. 2015. Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity. Nat. Med. 21:610–18
     [Google Scholar]
  45. 45.  Wang XA, Zhang R, Zhang S, Deng S, Jiang D et al. 2013. Interferon regulatory factor 7 deficiency prevents diet-induced obesity and insulin resistance. Am. J. Physiol. Endocrinol. Metab. 305:E485–95
     [Google Scholar]
  46. 46.  Higashi T, Friedman SL, Hoshida Y 2017. Hepatic stellate cells as key target in liver fibrosis. Adv. Drug Deliv. Rev. 121:27–42
     [Google Scholar]
  47. 47.  Reilly SM, Saltiel AR 2017. Adapting to obesity with adipose tissue inflammation. Nat. Rev. Endocrinol. 13:633–43
     [Google Scholar]
  48. 48.  Sanz Y, Moya-Perez A 2014. Microbiota, inflammation and obesity. Adv. Exp. Med. Biol. 817:291–317
     [Google Scholar]
  49. 49.  Caesar R, Tremaroli V, Kovatcheva-Datchary P, Cani PD, Backhed F 2015. Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling. Cell Metab 22:658–68
     [Google Scholar]
  50. 50.  Bjorkbacka H, Kunjathoor VV, Moore KJ, Koehn S, Ordija CM et al. 2004. Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways. Nat. Med. 10:416–21
     [Google Scholar]
  51. 51.  Richards MR, Black AS, Bonnet DJ, Barish GD, Woo CW et al. 2013. The LPS2 mutation in TRIF is atheroprotective in hyperlipidemic low density lipoprotein receptor knockout mice. Innate Immun 19:20–29
     [Google Scholar]
  52. 52.  Castoldi A, Andrade-Oliveira V, Aguiar CF, Amano MT, Lee J et al. 2017. Dectin-1 activation exacerbates obesity and insulin resistance in the absence of MyD88. Cell Rep 19:2272–88
     [Google Scholar]
  53. 53.  Larsson E, Tremaroli V, Lee YS, Koren O, Nookaew I et al. 2012. Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88. Gut 61:1124–31
     [Google Scholar]
  54. 54.  Schertzer JD, Tamrakar AK, Magalhaes JG, Pereira S, Bilan PJ et al. 2011. NOD1 activators link innate immunity to insulin resistance. Diabetes 60:2206–15
     [Google Scholar]
  55. 55.  Tamrakar AK, Schertzer JD, Chiu TT, Foley KP, Bilan PJ et al. 2010. NOD2 activation induces muscle cell–autonomous innate immune responses and insulin resistance. Endocrinology 151:5624–37
     [Google Scholar]
  56. 56.  Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K et al. 2011. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med. 17:179–88
     [Google Scholar]
  57. 57.  Stienstra R, van Diepen JA, Tack CJ, Zaki MH, van de Veerdonk FL et al. 2011. Inflammasome is a central player in the induction of obesity and insulin resistance. PNAS 108:15324–29
     [Google Scholar]
  58. 58.  Wen H, Gris D, Lei Y, Jha S, Zhang L et al. 2011. Fatty acid–induced NLRP3–ASC inflammasome activation interferes with insulin signaling. Nat. Immunol. 12:408–15
     [Google Scholar]
  59. 59.  Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G et al. 2010. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464:1357–61
     [Google Scholar]
  60. 60.  Shi Y, Evans JE, Rock KL 2003. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425:516–21
     [Google Scholar]
  61. 61.  Zambetti LP, Mortellaro A 2014. NLRPs, microbiota, and gut homeostasis: unravelling the connection. J. Pathol. 233:321–30
     [Google Scholar]
  62. 62.  Gaens KH, Goossens GH, Niessen PM, van Greevenbroek MM, van der Kallen CJ et al. 2014. Nε-(carboxymethyl)lysine–receptor for advanced glycation end product axis is a key modulator of obesity-induced dysregulation of adipokine expression and insulin resistance. Arterioscler. Thromb. Vasc. Biol. 34:1199–208
     [Google Scholar]
  63. 63.  Bierhaus A, Nawroth PP 2009. Multiple levels of regulation determine the role of the receptor for AGE (RAGE) as common soil in inflammation, immune responses and diabetes mellitus and its complications. Diabetologia 52:2251–63
     [Google Scholar]
  64. 64.  Song F, Hurtado del Pozo C, Rosario R, Zou YS, Ananthakrishnan R et al. 2014. RAGE regulates the metabolic and inflammatory response to high-fat feeding in mice. Diabetes 63:1948–65
     [Google Scholar]
  65. 65.  Palma-Duran SA, Kontogianni MD, Vlassopoulos A, Zhao S, Margariti A et al. 2018. Serum levels of advanced glycation end-products (AGEs) and the decoy soluble receptor for AGEs (sRAGE) can discriminate non-alcoholic fatty liver disease in age-, sex- and BMI-matched normo-glycemic adults. Metabolism 83:120–27
     [Google Scholar]
  66. 66.  Solinas G, Becattini B 2017. JNK at the crossroad of obesity, insulin resistance, and cell stress response. Mol. Metab. 6:174–84
     [Google Scholar]
  67. 67.  Lee KY, Russell SJ, Ussar S, Boucher J, Vernochet C et al. 2013. Lessons on conditional gene targeting in mouse adipose tissue. Diabetes 62:864–74
     [Google Scholar]
  68. 68.  Hacker H, Karin M 2006. Regulation and function of IKK and IKK-related kinases. Sci. STKE 2006:re13
     [Google Scholar]
  69. 69.  Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW et al. 2005. IKK-β links inflammation to obesity-induced insulin resistance. Nat. Med. 11:191–98
     [Google Scholar]
  70. 70.  Chiang SH, Bazuine M, Lumeng CN, Geletka LM, Mowers J et al. 2009. The protein kinase IKKε regulates energy balance in obese mice. Cell 138:961–75
     [Google Scholar]
  71. 71.  Mowers J, Uhm M, Reilly SM, Simon J, Leto D et al. 2013. Inflammation produces catecholamine resistance in obesity via activation of PDE3B by the protein kinases IKKε and TBK1. eLife 2:e01119
     [Google Scholar]
  72. 72.  Zhao P, Wong KI, Sun X, Reilly SM, Uhm M et al. 2018. TBK1 at the crossroads of inflammation and energy homeostasis in adipose tissue. Cell 172:731–43.e12
     [Google Scholar]
  73. 73.  Brestoff JR, Kim BS, Saenz SA, Stine RR, Monticelli LA et al. 2015. Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity. Nature 519:242–46
     [Google Scholar]
  74. 74.  Pal M, Febbraio MA, Lancaster GI 2016. The roles of c-Jun NH2-terminal kinases (JNKs) in obesity and insulin resistance. J. Physiol. 594:267–79
     [Google Scholar]
  75. 75.  Hotamisligil GS, Davis RJ 2016. Cell signaling and stress responses. Cold Spring Harb. Perspect. Biol. 8:a006072
     [Google Scholar]
  76. 76.  Eguchi J, Kong X, Tenta M, Wang X, Kang S, Rosen ED 2013. Interferon regulatory factor 4 regulates obesity-induced inflammation through regulation of adipose tissue macrophage polarization. Diabetes 62:3394–403
     [Google Scholar]
  77. 77.  Eguchi J, Wang X, Yu S, Kershaw EE, Chiu PC et al. 2011. Transcriptional control of adipose lipid handling by IRF4. Cell Metab 13:249–59
     [Google Scholar]
  78. 78.  Kong X, Banks A, Liu T, Kazak L, Rao RR et al. 2014. IRF4 is a key thermogenic transcriptional partner of PGC-1α. Cell 158:69–83
     [Google Scholar]
  79. 79.  Baker RG, Hayden MS, Ghosh S 2011. NF-κB, inflammation, and metabolic disease. Cell Metab 13:11–22
     [Google Scholar]
  80. 80.  Mishra PK, Ying W, Nandi SS, Bandyopadhyay GK, Patel KK, Mahata SK 2017. Diabetic cardiomyopathy: an immunometabolic perspective. Front. Endocrinol. 8:72
     [Google Scholar]
  81. 81.  Gistera A, Hansson GK 2017. The immunology of atherosclerosis. Nat. Rev. Nephrol. 13:368–80
     [Google Scholar]
  82. 82.  Goulopoulou S, McCarthy CG, Webb RC 2016. Toll-like receptors in the vascular system: sensing the dangers within. Pharmacol. Rev. 68:142–67
     [Google Scholar]
  83. 83.  Moore KJ, Tabas I 2011. Macrophages in the pathogenesis of atherosclerosis. Cell 145:341–55
     [Google Scholar]
  84. 84.  Jain M, Singh A, Singh V, Barthwal MK 2015. Involvement of interleukin-1 receptor–associated kinase-1 in vascular smooth muscle cell proliferation and neointimal formation after rat carotid injury. Arterioscler. Thromb. Vasc. Biol. 35:1445–55
     [Google Scholar]
  85. 85.  Rekhter M, Staschke K, Estridge T, Rutherford P, Jackson N et al. 2008. Genetic ablation of IRAK4 kinase activity inhibits vascular lesion formation. Biochem. Biophys. Res. Commun. 367:642–48
     [Google Scholar]
  86. 86.  Doyon P, Servant MJ 2010. Tumor necrosis factor receptor–associated factor-6 and ribosomal S6 kinase intracellular pathways link the angiotensin II AT1 receptor to the phosphorylation and activation of the IκB kinase complex in vascular smooth muscle cells. J. Biol. Chem. 285:30708–18
     [Google Scholar]
  87. 87.  Missiou A, Kostlin N, Varo N, Rudolf P, Aichele P et al. 2010. Tumor necrosis factor receptor–associated factor 1 (TRAF1) deficiency attenuates atherosclerosis in mice by impairing monocyte recruitment to the vessel wall. Circulation 121:2033–44
     [Google Scholar]
  88. 88.  Szilagyi K, Gijbels MJ, van der Velden S, Heinsbroek SE, Kraal G et al. 2015. Dectin-1 deficiency does not affect atherosclerosis development in mice. Atherosclerosis 239:318–21
     [Google Scholar]
  89. 89.  Kim YJ, Koo TY, Yang WS, Han NJ, Jeong JU et al. 2012. Activation of spleen tyrosine kinase is required for TNF-α-induced endothelin-1 upregulation in human aortic endothelial cells. FEBS Lett 586:818–26
     [Google Scholar]
  90. 90.  Kanno S, Nishio H, Tanaka T, Motomura Y, Murata K et al. 2015. Activation of an innate immune receptor, Nod1, accelerates atherogenesis in Apoe−/− mice. J. Immunol. 194:773–80
     [Google Scholar]
  91. 91.  Johansson ME, Zhang XY, Edfeldt K, Lundberg AM, Levin MC et al. 2014. Innate immune receptor NOD2 promotes vascular inflammation and formation of lipid-rich necrotic cores in hypercholesterolemic mice. Eur. J. Immunol. 44:3081–92
     [Google Scholar]
  92. 92.  Liu D, Zeng X, Li X, Mehta JL, Wang X 2017. Role of NLRP3 inflammasome in the pathogenesis of cardiovascular diseases. Basic Res. Cardiol. 113:5
     [Google Scholar]
  93. 93.  Hopkins PN 2013. Molecular biology of atherosclerosis. Physiol. Rev. 93:1317–542
     [Google Scholar]
  94. 94.  Xie P 2013. TRAF molecules in cell signaling and in human diseases. J. Mol. Signal. 8:7
     [Google Scholar]
  95. 95.  Missiou A, Rudolf P, Stachon P, Wolf D, Varo N et al. 2010. TRAF5 deficiency accelerates atherogenesis in mice by increasing inflammatory cell recruitment and foam cell formation. Circ. Res. 107:757–66
     [Google Scholar]
  96. 96.  Dong LH, Li L, Song Y, Duan ZL, Sun SG et al. 2015. TRAF6-mediated SM22α K21 ubiquitination promotes G6PD activation and NADPH production, contributing to GSH homeostasis and VSMC survival in vitro and in vivo. Circ. Res. 117:684–94
     [Google Scholar]
  97. 97.  Kierdorf K, Fritz G 2013. RAGE regulation and signaling in inflammation and beyond. J. Leukoc. Biol. 94:55–68
     [Google Scholar]
  98. 98.  Choe N, Kwon JS, Kim JR, Eom GH, Kim Y et al. 2013. The microRNA miR-132 targets Lrrfip1 to block vascular smooth muscle cell proliferation and neointimal hyperplasia. Atherosclerosis 229:348–55
     [Google Scholar]
  99. 99.  Medunjanin S, Daniel JM, Weinert S, Dutzmann J, Burgbacher F et al. 2015. DNA-dependent protein kinase (DNA-PK) permits vascular smooth muscle cell proliferation through phosphorylation of the orphan nuclear receptor NOR1. Cardiovasc. Res. 106:488–97
     [Google Scholar]
  100. 100.  Lin Y, Zhu X, McLntee FL, Xiao H, Zhang J et al. 2004. Interferon regulatory factor-1 mediates PPARγ-induced apoptosis in vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 24:257–63.
     [Google Scholar]
  101. 101.  Huang L, Zhang SM, Zhang P, Zhang XJ, Zhu LH et al. 2014. Interferon regulatory factor 7 protects against vascular smooth muscle cell proliferation and neointima formation. J. Am. Heart Assoc. 3:e001309
     [Google Scholar]
  102. 102.  Zhang SM, Zhu LH, Chen HZ, Zhang R, Zhang P et al. 2014. Interferon regulatory factor 9 is critical for neointima formation following vascular injury. Nat. Commun. 5:5160
     [Google Scholar]
  103. 103.  Zhang SM, Zhu LH, Li ZZ, Wang PX, Chen HZ et al. 2014. Interferon regulatory factor 3 protects against adverse neo-intima formation. Cardiovasc. Res. 102:469–79
     [Google Scholar]
  104. 104.  Liu H, Cheng WL, Jiang X, Wang PX, Fang C et al. 2017. Ablation of interferon regulatory factor 3 protects against atherosclerosis in apolipoprotein E–deficient mice. Hypertension 69:510–20
     [Google Scholar]
  105. 105.  Zhang SM, Gao L, Zhang XF, Zhang R, Zhu LH et al. 2014. Interferon regulatory factor 8 modulates phenotypic switching of smooth muscle cells by regulating the activity of myocardin. Mol. Cell. Biol. 34:400–14
     [Google Scholar]
  106. 106.  Doring Y, Soehnlein O, Drechsler M, Shagdarsuren E, Chaudhari SM et al. 2012. Hematopoietic interferon regulatory factor 8-deficiency accelerates atherosclerosis in mice. Arterioscler. Thromb. Vasc. Biol. 32:1613–23
     [Google Scholar]
  107. 107.  Li Y, Si R, Feng Y, Chen HH, Zou L et al. 2011. Myocardial ischemia activates an injurious innate immune signaling via cardiac heat shock protein 60 and Toll-like receptor 4. J. Biol. Chem. 286:31308–19
     [Google Scholar]
  108. 108.  Yang YF, Chen Z, Hu SL, Hu J, Li B et al. 2011. Interleukin-1 receptor associated kinases-1/4 inhibition protects against acute hypoxia/ischemia-induced neuronal injury in vivo and in vitro. Neuroscience 196:25–34
     [Google Scholar]
  109. 109.  White BJ, Tarabishy S, Venna VR, Manwani B, Benashski S et al. 2012. Protection from cerebral ischemia by inhibition of TGFβ-activated kinase. Exp. Neurol. 237:238–45
     [Google Scholar]
  110. 110.  Iadecola C, Salkowski CA, Zhang F, Aber T, Nagayama M et al. 1999. The transcription factor interferon regulatory factor 1 is expressed after cerebral ischemia and contributes to ischemic brain injury. J. Exp. Med. 189:719–27
     [Google Scholar]
  111. 111.  Alexander M, Forster C, Sugimoto K, Clark HB, Vogel S et al. 2003. Interferon regulatory factor-1 immunoreactivity in neurons and inflammatory cells following ischemic stroke in rodents and humans. Acta Neuropathol 105:420–24
     [Google Scholar]
  112. 112.  Stevens SL, Leung PY, Vartanian KB, Gopalan B, Yang T et al. 2011. Multiple preconditioning paradigms converge on interferon regulatory factor–dependent signaling to promote tolerance to ischemic brain injury. J. Neurosci. 31:8456–63
     [Google Scholar]
  113. 113.  Xiang M, Wang L, Guo S, Lu YY, Lei H et al. 2014. Interferon regulatory factor 8 protects against cerebral ischaemic–reperfusion injury. J. Neurochem. 129:988–1001
     [Google Scholar]
  114. 114.  Yang H, Li N, Song LN, Wang L, Tian C et al. 2015. Activation of NOD1 by DAP contributes to myocardial ischemia/reperfusion injury via multiple signaling pathways. Apoptosis 20:512–22
     [Google Scholar]
  115. 115.  Andrassy M, Volz HC, Igwe JC, Funke B, Eichberger SN et al. 2008. High-mobility group box-1 in ischemia–reperfusion injury of the heart. Circulation 117:3216–26
     [Google Scholar]
  116. 116.  Fann DY, Lee SY, Manzanero S, Tang SC, Gelderblom M et al. 2013. Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome–mediated neuronal death in ischemic stroke. Cell Death Dis 4:e790
     [Google Scholar]
  117. 117.  Denes A, Coutts G, Lenart N, Cruickshank SM, Pelegrin P et al. 2015. AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3. PNAS 112:4050–55
     [Google Scholar]
  118. 118.  Kawaguchi M, Takahashi M, Hata T, Kashima Y, Usui F et al. 2011. Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury. Circulation 123:594–604
     [Google Scholar]
  119. 119.  Chen C, Feng Y, Zou L, Wang L, Chen HH et al. 2014. Role of extracellular RNA and TLR3–Trif signaling in myocardial ischemia–reperfusion injury. J. Am. Heart Assoc. 3:e000683
     [Google Scholar]
  120. 120.  Pourrajab F, Yazdi MB, Zarch MB, Zarch MB, Hekmatimoghaddam S 2015. Cross talk of the first-line defense TLRs with PI3K/Akt pathway, in preconditioning therapeutic approach. Mol. Cell. Ther. 3:4
     [Google Scholar]
  121. 121.  Lu YY, Li ZZ, Jiang DS, Wang L, Zhang Y et al. 2013. TRAF1 is a critical regulator of cerebral ischaemia–reperfusion injury and neuronal death. Nat. Commun. 4:2852
     [Google Scholar]
  122. 122.  Gong J, Li ZZ, Guo S, Zhang XJ, Zhang P et al. 2015. Neuron-specific tumor necrosis factor receptor–associated factor 3 is a central regulator of neuronal death in acute ischemic stroke. Hypertension 66:604–16
     [Google Scholar]
  123. 123.  Wang L, Lu Y, Guan H, Jiang D, Guan Y et al. 2013. Tumor necrosis factor receptor–associated factor 5 is an essential mediator of ischemic brain infarction. J. Neurochem. 126:400–14
     [Google Scholar]
  124. 124.  Tzeng HP, Evans S, Gao F, Chambers K, Topkara VK et al. 2014. Dysferlin mediates the cytoprotective effects of TRAF2 following myocardial ischemia reperfusion injury. J. Am. Heart Assoc. 3:e000662
     [Google Scholar]
  125. 125.  Yang KC, Ma X, Liu H, Murphy J, Barger PM et al. 2015. Tumor necrosis factor receptor–associated factor 2 mediates mitochondrial autophagy. Circ. Heart Fail. 8:175–87
     [Google Scholar]
  126. 126.  Li L, Qin JJ, Guo S, Zhang P, Gong J et al. 2015. Attenuation of cerebral ischemic injury in interferon regulatory factor 3–deficient rat. J. Neurochem. 136:871–83
     [Google Scholar]
  127. 127.  Guo S, Li ZZ, Jiang DS, Lu YY, Liu Y et al. 2014. IRF4 is a novel mediator for neuronal survival in ischaemic stroke. Cell Death Differ 21:888–903
     [Google Scholar]
  128. 128.  Wang PX, Zhang R, Huang L, Zhu LH, Jiang DS et al. 2015. Interferon regulatory factor 9 is a key mediator of hepatic ischemia/reperfusion injury. J. Hepatol. 62:111–20
     [Google Scholar]
  129. 129.  Chen HZ, Guo S, Li ZZ, Lu Y, Jiang DS et al. 2014. A critical role for interferon regulatory factor 9 in cerebral ischemic stroke. J. Neurosci. 34:11897–912
     [Google Scholar]
  130. 130.  Zhang Y, Liu X, She ZG, Jiang DS, Wan N et al. 2014. Interferon regulatory factor 9 is an essential mediator of heart dysfunction and cell death following myocardial ischemia/reperfusion injury. Basic Res. Cardiol. 109:434
     [Google Scholar]
  131. 131.  Zuurbier CJ, Jong WM, Eerbeek O, Koeman A, Pulskens WP et al. 2012. Deletion of the innate immune NLRP3 receptor abolishes cardiac ischemic preconditioning and is associated with decreased Il-6/STAT3 signaling. PLOS ONE 7:e40643
     [Google Scholar]
  132. 132.  Bruchard M, Rebe C, Derangere V, Togbe D, Ryffel B et al. 2015. The receptor NLRP3 is a transcriptional regulator of TH2 differentiation. Nat. Immunol. 16:859–70
     [Google Scholar]
  133. 133.  Suzuki Y, Nakano Y, Mishiro K, Takagi T, Tsuruma K et al. 2013. Involvement of Mincle and Syk in the changes to innate immunity after ischemic stroke. Sci. Rep. 3:3177
     [Google Scholar]
  134. 134.  Hayden MS, Ghosh S 2008. Shared principles in NF-κB signaling. Cell 132:344–62
     [Google Scholar]
  135. 135.  Singh MV, Cicha MZ, Meyerholz DK, Chapleau MW, Abboud FM 2015. Dual activation of TRIF and MyD88 adaptor proteins by angiotensin II evokes opposing effects on pressure, cardiac hypertrophy, and inflammatory gene expression. Hypertension 66:647–56
     [Google Scholar]
  136. 136.  Ramasamy R, Schmidt AM 2012. Receptor for advanced glycation end products (RAGE) and implications for the pathophysiology of heart failure. Curr. Heart Fail. Rep. 9:107–16
     [Google Scholar]
  137. 137.  Bracey NA, Gershkovich B, Chun J, Vilaysane A, Meijndert HC et al. 2014. Mitochondrial NLRP3 protein induces reactive oxygen species to promote Smad protein signaling and fibrosis independent from the inflammasome. J. Biol. Chem. 289:19571–84
     [Google Scholar]
  138. 138.  Val-Blasco A, Piedras M, Ruiz-Hurtado G, Suarez N, Prieto P et al. 2017. Role of NOD1 in heart failure progression via regulation of Ca2+ handling. J. Am. Coll. Cardiol. 69:423–33
     [Google Scholar]
  139. 139.  Huang Y, Wu D, Zhang X, Jiang M, Hu C et al. 2014. Cardiac-specific Traf2 overexpression enhances cardiac hypertrophy through activating AKT/GSK3β signaling. Gene 536:225–31
     [Google Scholar]
  140. 140.  Guo X, Yin H, Li L, Chen Y, Li J et al. 2017. Cardioprotective role of TRAF2 by suppressing apoptosis and necroptosis. Circulation 136:729–42
     [Google Scholar]
  141. 141.  Bian Z, Dai J, Hiroyasu N, Guan H, Yuan Y et al. 2014. Disruption of tumor necrosis factor receptor associated factor 5 exacerbates pressure overload cardiac hypertrophy and fibrosis. J. Cell. Biochem. 115:349–58
     [Google Scholar]
  142. 142.  Ji YX, Zhang P, Zhang XJ, Zhao YC, Deng KQ et al. 2016. The ubiquitin E3 ligase TRAF6 exacerbates pathological cardiac hypertrophy via TAK1-dependent signalling. Nat. Commun. 7:11267
     [Google Scholar]
  143. 143.  Lu J, Bian ZY, Zhang R, Zhang Y, Liu C et al. 2013. Interferon regulatory factor 3 is a negative regulator of pathological cardiac hypertrophy. Basic Res. Cardiol. 108:326
     [Google Scholar]
  144. 144.  Jiang DS, Liu Y, Zhou H, Zhang Y, Zhang XD et al. 2014. Interferon regulatory factor 7 functions as a novel negative regulator of pathological cardiac hypertrophy. Hypertension 63:713–22
     [Google Scholar]
  145. 145.  Jiang DS, Wei X, Zhang XF, Liu Y, Zhang Y et al. 2014. IRF8 suppresses pathological cardiac remodelling by inhibiting calcineurin signalling. Nat. Commun. 5:3303
     [Google Scholar]
  146. 146.  Jiang DS, Luo YX, Zhang R, Zhang XD, Chen HZ et al. 2014. Interferon regulatory factor 9 protects against cardiac hypertrophy by targeting myocardin. Hypertension 63:119–27
     [Google Scholar]
  147. 147.  Jin C, Henao-Mejia J, Flavell RA 2013. Innate immune receptors: key regulators of metabolic disease progression. Cell Metab 17:873–82
     [Google Scholar]
  148. 148.  Fuster JJ, Walsh K 2018. Somatic mutations and clonal hematopoiesis: unexpected potential new drivers of age-related cardiovascular disease. Circ. Res. 122:523–32
     [Google Scholar]
  149. 149.  Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG et al. 2017. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N. Engl. J. Med. 377:111–21
     [Google Scholar]
  150. 150.  Fuster JJ, MacLauchlan S, Zuriaga MA, Polackal MN, Ostriker AC et al. 2017. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science 355:842–47
     [Google Scholar]
  151. 151.  Baylis RA, Gomez D, Mallat Z, Pasterkamp G, Owens GK 2017. The CANTOS trial: one important step for clinical cardiology but a giant leap for vascular biology. Arterioscler. Thromb. Vasc. Biol. 37:e174–e77
     [Google Scholar]
  152. 152.  Tacke F 2017. Targeting hepatic macrophages to treat liver diseases. J. Hepatol. 66:1300–12
     [Google Scholar]
  153. 153.  Konerman MA, Jones JC, Harrison SA 2018. Pharmacotherapy for NASH: current and emerging. J. Hepatol. 68:362–75
     [Google Scholar]
  154. 154.  Peterson KR, Cottam MA, Kennedy AJ, Hasty AH 2018. Macrophage-targeted therapeutics for metabolic disease. Trends Pharmacol. Sci. 39:536–46
     [Google Scholar]
/content/journals/10.1146/annurev-pathmechdis-012418-013003
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Innate Immune Signaling in Nonalcoholic Fatty Liver Disease and Cardiovascular Diseases
Annual Review of Pathology: Mechanisms of Disease 14, 153 (2019); https://doi.org/10.1146/annurev-pathmechdis-012418-013003
/content/journals/10.1146/annurev-pathmechdis-012418-013003
/content/journals/10.1146/annurev-pathmechdis-012418-013003
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