1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Immunology
  4. Volume 37, 2019
  5. Article

Annual Review of Immunology

Volume 37, 2019

Disease Tolerance as an Inherent Component of Immunity

Abstract

Pathogenic organisms exert a negative impact on host health, revealed by the clinical signs of infectious diseases. Immunity limits the severity of infectious diseases through resistance mechanisms that sense and target pathogens for containment, killing, or expulsion. These resistance mechanisms are viewed as the prevailing function of immunity. Under pathophysiologic conditions, however, immunity arises in response to infections that carry health and fitness costs to the host. Therefore, additional defense mechanisms are required to limit these costs, before immunity becomes operational as well as thereafter to avoid immunopathology. These are tissue damage control mechanisms that adjust the metabolic output of host tissues to different forms of stress and damage associated with infection. Disease tolerance is the term used to define this defense strategy, which does not exert a direct impact on pathogens but is essential to limit the health and fitness costs of infection. Under this argument, we propose that disease tolerance is an inherent component of immunity.

Keyword(s): damage, disease tolerance, immunoregulation, infection, metabolism, microbiota, nutritional immunity, stress, tissue damage control
Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-042718-041739
2019-04-26
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/immunol/37/1/annurev-immunol-042718-041739.html?itemId=/content/journals/10.1146/annurev-immunol-042718-041739&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Schaefer JF 1971. Tolerance to plant disease. Annu. Rev. Phytopathol. 9:235–52
     [Google Scholar]
  2. 2.
    Cobb NA 1894. Contributions to an economic knowledge of Australian rusts (Uredineae): improving wheat by selection Dep. Agric. N.S.W. Sydney: C. Potter
  3. 3.
    Medzhitov R, Schneider D, Soares M 2012. Disease tolerance as a defense strategy. Science 335:936–41
     [Google Scholar]
  4. 4.
    Schneider DS, Ayres JS 2008. Two ways to survive infection: what resistance and tolerance can teach us about treating infectious diseases. Nat. Rev. Immunol. 8:889–95
     [Google Scholar]
  5. 5.
    Ayres JS, Freitag N, Schneider DS 2008. Identification of Drosophila mutants altering defense of and endurance to Listeria monocytogenes infection. Genetics 178:1807–15
     [Google Scholar]
  6. 6.
    Teixeira L, Ferreira A, Ashburner M 2008. The bacterial symbiont Wolbachia induces resistance to RNA viral infections in Drosophila melanogaster. . PLOS Biol 6:e2
     [Google Scholar]
  7. 7.
    Raberg L, Sim D, Read AF 2007. Disentangling genetic variation for resistance and tolerance to infectious diseases in animals. Science 318:812–14
     [Google Scholar]
  8. 8.
    Seixas E, Gozzelino R, Chora A, Ferreira A, Silva G et al. 2009. Heme oxygenase-1 affords protection against noncerebral forms of severe malaria. PNAS 106:15837–42
     [Google Scholar]
  9. 9.
    Gozzelino R, Andrade BB, Larsen R, Luz NF, Vanoaica L et al. 2012. Metabolic adaptation to tissue iron overload confers tolerance to malaria. Cell Host Microbe 12:693–704
     [Google Scholar]
  10. 10.
    Scully JL 2004. What is a disease?. EMBO Rep 5:650–53
     [Google Scholar]
  11. 11.
    Shakhar K, Shakhar G 2015. Why do we feel sick when infected—can altruism play a role?. PLOS Biol 13:e1002276
     [Google Scholar]
  12. 12.
    Soares MP, Gozzelino R, Weis S 2014. Tissue damage control in disease tolerance. Trends Immunol 35:483–94
     [Google Scholar]
  13. 13.
    Davies KJ 2016. Adaptive homeostasis. Mol. Aspects Med. 49:1–7
     [Google Scholar]
  14. 14.
    Chovatiya R, Medzhitov R 2014. Stress, inflammation, and defense of homeostasis. Mol. Cell 54:281–88
     [Google Scholar]
  15. 15.
    Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW 2008. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat. Rev. Neurosci. 9:46–56
     [Google Scholar]
  16. 16.
    Rao S, Schieber AMP, O'Connor CP, Leblanc M, Michel D, Ayres JS 2017. Pathogen-mediated inhibition of anorexia promotes host survival and transmission. Cell 168:503–16.e12
     [Google Scholar]
  17. 17.
    Ferreira A, Marguti I, Bechmann I, Jeney V, Chora A et al. 2011. Sickle hemoglobin confers tolerance to Plasmodium infection. Cell 145:398–409
     [Google Scholar]
  18. 18.
    Soares MP, Teixeira L, Moita LF 2017. Disease tolerance and immunity in host protection against infection. Nat. Rev. Immunol. 17:83–96
     [Google Scholar]
  19. 19.
    Drakesmith H, Prentice AM 2012. Hepcidin and the iron-infection axis. Science 338:768–72
     [Google Scholar]
  20. 20.
    Weinberg ED 1975. Nutritional immunity: host's attempt to withold iron from microbial invaders. JAMA 231:39–41
     [Google Scholar]
  21. 21.
    Nunez G, Sakamoto K, Soares MP 2018. Innate nutritional immunity. J. Immunol. 201:11–18
     [Google Scholar]
  22. 22.
    Soares MP, Weiss G 2015. The Iron age of host-microbe interactions. EMBO Rep 16:1482–500
     [Google Scholar]
  23. 23.
    Weis S, Carlos AR, Moita MR, Singh S, Blankenhaus B et al. 2017. Metabolic adaptation establishes disease tolerance to sepsis. Cell 169:1263–75
     [Google Scholar]
  24. 24.
    Buck MD, Sowell RT, Kaech SM, Pearce EL 2017. Metabolic instruction of immunity. Cell 169:570–86
     [Google Scholar]
  25. 25.
    Kultz D 2005. Molecular and evolutionary basis of the cellular stress response. Annu. Rev. Physiol. 67:225–57
     [Google Scholar]
  26. 26.
    Lopez-Maury L, Marguerat S, Bahler J 2008. Tuning gene expression to changing environments: from rapid responses to evolutionary adaptation. Nat. Rev. Genet. 9:583–93
     [Google Scholar]
  27. 27.
    Kultz D 2003. Evolution of the cellular stress proteome: from monophyletic origin to ubiquitous function. J. Exp. Biol. 206:3119–24
     [Google Scholar]
  28. 28.
    Kotas ME, Medzhitov R 2015. Homeostasis, inflammation, and disease susceptibility. Cell 160:816–27
     [Google Scholar]
  29. 29.
    Hayes JD, Dinkova-Kostova AT 2014. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem. Sci. 39:199–218
     [Google Scholar]
  30. 30.
    Suzuki T, Motohashi H, Yamamoto M 2013. Toward clinical application of the Keap1-Nrf2 pathway. Trends Pharmacol. Sci. 34:340–46
     [Google Scholar]
  31. 31.
    Eltzschig HK, Carmeliet P 2011. Hypoxia and inflammation. N. Engl. J. Med. 364:656–65
     [Google Scholar]
  32. 32.
    Cramer T, Yamanishi Y, Clausen BE, Forster I, Pawlinski R et al. 2003. HIF-1α is essential for myeloid cell-mediated inflammation. Cell 112:645–57
     [Google Scholar]
  33. 33.
    Brocker C, Thompson DC, Vasiliou V 2012. The role of hyperosmotic stress in inflammation and disease. Biomol. Concepts 3:345–64
     [Google Scholar]
  34. 34.
    Aramburu J, Drews-Elger K, Estrada-Gelonch A, Minguillon J, Morancho B et al. 2006. Regulation of the hypertonic stress response and other cellular functions by the Rel-like transcription factor NFAT5. Biochem. Pharmacol. 72:1597–604
     [Google Scholar]
  35. 35.
    Moura-Alves P, Fae K, Houthuys E, Dorhoi A, Kreuchwig A et al. 2014. AhR sensing of bacterial pigments regulates antibacterial defence. Nature 512:387–92
     [Google Scholar]
  36. 36.
    Stockinger B, Di Meglio P, Gialitakis M, Duarte JH 2014. The aryl hydrocarbon receptor: multitasking in the immune system. Annu. Rev. Immunol. 32:403–32
     [Google Scholar]
  37. 37.
    Bessede A, Gargaro M, Pallotta MT, Matino D, Servillo G et al. 2014. Aryl hydrocarbon receptor control of a disease tolerance defence pathway. Nature 511:184–90
     [Google Scholar]
  38. 38.
    Postic C, Dentin R, Denechaud PD, Girard J 2007. ChREBP, a transcriptional regulator of glucose and lipid metabolism. Annu. Rev. Nutr. 27:179–92
     [Google Scholar]
  39. 39.
    Altarejos JY, Montminy M 2011. CREB and the CRTC co-activators: sensors for hormonal and metabolic signals. Nat. Rev. Mol. Cell Biol. 12:141–51
     [Google Scholar]
  40. 40.
    Efeyan A, Comb WC, Sabatini DM 2015. Nutrient-sensing mechanisms and pathways. Nature 517:302–10
     [Google Scholar]
  41. 41.
    Kilberg MS, Pan YX, Chen H, Leung-Pineda V 2005. Nutritional control of gene expression: how mammalian cells respond to amino acid limitation. Annu. Rev. Nutr. 25:59–85
     [Google Scholar]
  42. 42.
    Ravindran R, Loebbermann J, Nakaya HI, Khan N, Ma H et al. 2016. The amino acid sensor GCN2 controls gut inflammation by inhibiting inflammasome activation. Nature 531:523–27
     [Google Scholar]
  43. 43.
    Ang Z, Ding JL 2016. GPR41 and GPR43 in obesity and inflammation—protective or causative?. Front. Immunol. 7:28
     [Google Scholar]
  44. 44.
    Eijkelenboom A, Burgering BM 2013. FOXOs: signalling integrators for homeostasis maintenance. Nat. Rev. Mol. Cell Biol. 14:83–97
     [Google Scholar]
  45. 45.
    Dionne MS, Pham LN, Shirasu-Hiza M, Schneider DS 2006. Akt and FOXO dysregulation contribute to infection-induced wasting in Drosophila. Curr. . Biol 16:1977–85
     [Google Scholar]
  46. 46.
    Walter P, Ron D 2011. The unfolded protein response: from stress pathway to homeostatic regulation. Science 334:1081–86
     [Google Scholar]
  47. 47.
    Buchberger A, Bukau B, Sommer T 2010. Protein quality control in the cytosol and the endoplasmic reticulum: brothers in arms. Mol. Cell 40:238–52
     [Google Scholar]
  48. 48.
    Lindquist S 1986. The heat-shock response. Annu. Rev. Biochem. 55:1151–91
     [Google Scholar]
  49. 49.
    Richter K, Haslbeck M, Buchner J 2010. The heat shock response: life on the verge of death. Mol. Cell 40:253–66
     [Google Scholar]
  50. 50.
    Richardson CE, Kooistra T, Kim DH 2010. An essential role for XBP-1 in host protection against immune activation in C. elegans. . Nature 463:1092–95
     [Google Scholar]
  51. 51.
    Esposito V, Grosjean F, Tan J, Huang L, Zhu L et al. 2013. CHOP deficiency results in elevated lipopolysaccharide-induced inflammation and kidney injury. Am. J. Physiol. Renal Physiol. 304:F440–50
     [Google Scholar]
  52. 52.
    Wang A, Huen SC, Luan HH, Yu S, Zhang C et al. 2016. Opposing effects of fasting metabolism on tissue tolerance in bacterial and viral inflammation. Cell 166:1512–25.e12
     [Google Scholar]
  53. 53.
    Blackford AN, Jackson SP 2017. ATM, ATR, and DNA-PK: the trinity at the heart of the DNA damage response. Mol. Cell 66:801–17
     [Google Scholar]
  54. 54.
    Kruiswijk F, Labuschagne CF, Vousden KH 2015. p53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nat. Rev. Mol. Cell Biol. 16:393–405
     [Google Scholar]
  55. 55.
    Michan S, Sinclair D 2007. Sirtuins in mammals: insights into their biological function. Biochem. J. 404:1–13
     [Google Scholar]
  56. 56.
    Pamplona A, Ferreira A, Balla J, Jeney V, Balla G et al. 2007. Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria. Nat. Med. 13:703–10
     [Google Scholar]
  57. 57.
    Jeney V, Ramos S, Bergman ML, Bechmann I, Tischer J et al. 2014. Control of disease tolerance to malaria by nitric oxide and carbon monoxide. Cell Rep 8:126–36
     [Google Scholar]
  58. 58.
    Larsen R, Gozzelino R, Jeney V, Tokaji L, Bozza FA et al. 2010. A central role for free heme in the pathogenesis of severe sepsis. Sci. Transl. Med. 2:51ra71
     [Google Scholar]
  59. 59.
    Gozzelino R, Jeney V, Soares MP 2010. Mechanisms of cell protection by heme oxygenase-1. Annu. Rev. Pharmacol. Toxicol. 50:323–54
     [Google Scholar]
  60. 60.
    Bach FH 2005. Heme oxygenase-1: a therapeutic amplification funnel. FASEB J 19:1216–19
     [Google Scholar]
  61. 61.
    Soares MP, Bach FH 2009. Heme oxygenase-1: from biology to therapeutic potential. Trends Mol. Med. 15:50–58
     [Google Scholar]
  62. 62.
    Otterbein LE, Bach FH, Alam J, Soares MP, Tao HL et al. 2000. Carbon monoxide mediates anti-inflammatory effects via the mitogen activated protein kinase pathway. Nat. Med. 6:422–28
     [Google Scholar]
  63. 63.
    Brouard S, Otterbein LE, Anrather J, Tobiasch E, Bach FH et al. 2000. Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. J. Exp. Med. 192:1015–26
     [Google Scholar]
  64. 64.
    Otterbein LE, Zuckerbraun BS, Haga M, Liu F, Song R et al. 2003. Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nat. Med. 9:183–90
     [Google Scholar]
  65. 65.
    Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN 1987. Bilirubin is an antioxidant of possible physiological importance. Science 235:1043–46
     [Google Scholar]
  66. 66.
    Elledge SJ 1996. Cell cycle checkpoints: preventing an identity crisis. Science 274:1664–72
     [Google Scholar]
  67. 67.
    Johnson DG, Walker CL 1999. Cyclins and cell cycle checkpoints. Annu. Rev. Pharmacol. Toxicol. 39:295–312
     [Google Scholar]
  68. 68.
    Abbas T, Dutta A 2009. p21 in cancer: intricate networks and multiple activities. Nat. Rev. Cancer 9:400–14
     [Google Scholar]
  69. 69.
    Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S 2004. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu. Rev. Biochem. 73:39–85
     [Google Scholar]
  70. 70.
    Rashidian J, Iyirhiaro G, Aleyasin H, Rios M, Vincent I et al. 2005. Multiple cyclin-dependent kinases signals are critical mediators of ischemia/hypoxic neuronal death in vitro and in vivo. PNAS 102:14080–85
     [Google Scholar]
  71. 71.
    Medzhitov R 2008. Origin and physiological roles of inflammation. Nature 454:428–35
     [Google Scholar]
  72. 72.
    Gillet G, Brun G 1996. Viral inhibition of apoptosis. Trends Microbiol 4:312–17
     [Google Scholar]
  73. 73.
    Randow F, MacMicking JD, James LC 2013. Cellular self-defense: how cell-autonomous immunity protects against pathogens. Science 340:701–6
     [Google Scholar]
  74. 74.
    Kuriakose T, Man SM, Subbarao Malireddi RK, Karki R, Kesavardhana S et al. 2016. ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Sci. Immunol. 1:aag2045
     [Google Scholar]
  75. 75.
    Vereecke L, Beyaert R, van Loo G 2011. Enterocyte death and intestinal barrier maintenance in ho-meostasis and disease. Trends Mol. Med. 17:584–93
     [Google Scholar]
  76. 76.
    Sellin ME, Muller AA, Felmy B, Dolowschiak T, Diard M et al. 2014. Epithelium-intrinsic NAIP/NLRC4 inflammasome drives infected enterocyte expulsion to restrict Salmonella replication in the intestinal mucosa. Cell Host Microbe 16:237–48
     [Google Scholar]
  77. 77.
    Nordlander S, Pott J, Maloy KJ 2014. NLRC4 expression in intestinal epithelial cells mediates protection against an enteric pathogen. Mucosal Immunol 7:775–85
     [Google Scholar]
  78. 78.
    Buchon N, Broderick NA, Chakrabarti S, Lemaitre B 2009. Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. . Genes Dev 23:2333–44
     [Google Scholar]
  79. 79.
    Karin M, Clevers H 2016. Reparative inflammation takes charge of tissue regeneration. Nature 529:307–15
     [Google Scholar]
  80. 80.
    Dotiwala F, Mulik S, Polidoro RB, Ansara JA, Burleigh BA et al. 2016. Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites. Nat. Med. 22:210–16
     [Google Scholar]
  81. 81.
    Walch M, Dotiwala F, Mulik S, Thiery J, Kirchhausen T et al. 2014. Cytotoxic cells kill intracellular bacteria through granulysin-mediated delivery of granzymes. Cell 157:1309–23
     [Google Scholar]
  82. 82.
    Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y et al. 2004. Neutrophil extracellular traps kill bacteria. Science 303:1532–35
     [Google Scholar]
  83. 83.
    Kaplan MJ, Radic M 2012. Neutrophil extracellular traps: double-edged swords of innate immunity. J. Immunol. 189:2689–95
     [Google Scholar]
  84. 84.
    Iwasaki A, Medzhitov R 2015. Control of adaptive immunity by the innate immune system. Nat. Immunol. 16:343–53
     [Google Scholar]
  85. 85.
    Lazar-Molnar E, Chen B, Sweeney KA, Wang EJ, Liu W et al. 2010. Programmed death-1 (PD-1)-deficient mice are extraordinarily sensitive to tuberculosis. PNAS 107:13402–7
     [Google Scholar]
  86. 86.
    Tzelepis F, Blagih J, Khan N, Gillard J, Mendonca L et al. 2018. Mitochondrial cyclophilin D regulates T cell metabolic responses and disease tolerance to tuberculosis. Sci. Immunol. 3:eaar4135
     [Google Scholar]
  87. 87.
    Brandes M, Klauschen F, Kuchen S, Germain RN 2013. A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection. Cell 154:197–212
     [Google Scholar]
  88. 88.
    Kang E, Zhou G, Yousefi M, Cayrol R, Xia J, Gruenheid S 2018. Loss of disease tolerance during Citrobacter rodentium infection is associated with impaired epithelial differentiation and hyperactivation of T cell responses. Sci. Rep. 8:847
     [Google Scholar]
  89. 89.
    Sercundes MK, Ortolan LS, Debone D, Soeiro-Pereira PV, Gomes E et al. 2016. Targeting neutrophils to prevent malaria-associated acute lung injury/acute respiratory distress syndrome in mice. PLOS Pathog 12:e1006054
     [Google Scholar]
  90. 90.
    Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ et al. 2001. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 27:20–21
     [Google Scholar]
  91. 91.
    Fontenot JD, Gavin MA, Rudensky AY 2003. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4:330–36
     [Google Scholar]
  92. 92.
    Josefowicz SZ, Lu LF, Rudensky AY 2012. Regulatory T cells: mechanisms of differentiation and function. Annu. Rev. Immunol. 30:531–64
     [Google Scholar]
  93. 93.
    Schmidt A, Oberle N, Krammer PH 2012. Molecular mechanisms of Treg-mediated T cell suppression. Front. Immunol. 3:51
     [Google Scholar]
  94. 94.
    Liu Z, Gerner MY, Van Panhuys N, Levine AG, Rudensky AY, Germain RN 2015. Immune homeostasis enforced by co-localized effector and regulatory T cells. Nature 528:225–30
     [Google Scholar]
  95. 95.
    Germain RN 2012. Maintaining system homeostasis: the third law of Newtonian immunology. Nat. Immunol. 13:902–6
     [Google Scholar]
  96. 96.
    Kurup SP, Obeng-Adjei N, Anthony SM, Traore B, Doumbo OK et al. 2017. Regulatory T cells impede acute and long-term immunity to blood-stage malaria through CTLA-4. Nat. Med. 23:1220–25
     [Google Scholar]
  97. 97.
    Dittmer U, He H, Messer RJ, Schimmer S, Olbrich AR et al. 2004. Functional impairment of CD8+ T cells by regulatory T cells during persistent retroviral infection. Immunity 20:293–303
     [Google Scholar]
  98. 98.
    Maizels RM, McSorley HJ 2016. Regulation of the host immune system by helminth parasites. J. Allergy Clin. Immunol. 138:666–75
     [Google Scholar]
  99. 99.
    Suvas S, Azkur AK, Kim BS, Kumaraguru U, Rouse BT 2004. CD4+CD25+ regulatory T cells control the severity of viral immunoinflammatory lesions. J. Immunol. 172:4123–32
     [Google Scholar]
  100. 100.
    Li C, Corraliza I, Langhorne J 1999. A defect in interleukin-10 leads to enhanced malarial disease in Plasmodium chabaudi chabaudi infection in mice. Infect. Immun 67:4435–42
     [Google Scholar]
  101. 101.
    Kastenmuller W, Gasteiger G, Subramanian N, Sparwasser T, Busch DH et al. 2011. Regulatory T cells selectively control CD8+ T cell effector pool size via IL-2 restriction. J. Immunol. 187:3186–97
     [Google Scholar]
  102. 102.
    Xu M, Pokrovskii M, Ding Y, Yi R, Au C et al. 2018. c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont. Nature 554:373–77
     [Google Scholar]
  103. 103.
    Cornberg M, Kenney LL, Chen AT, Waggoner SN, Kim SK et al. 2013. Clonal exhaustion as a mechanism to protect against severe immunopathology and death from an overwhelming CD8 T cell response. Front. Immunol. 4:475
     [Google Scholar]
  104. 104.
    Wherry EJ, Kurachi M 2015. Molecular and cellular insights into T cell exhaustion. Nat. Rev. Immunol. 15:486–99
     [Google Scholar]
  105. 105.
    Hafalla JC, Claser C, Couper KN, Grau GE, Renia L et al. 2012. The CTLA-4 and PD-1/PD-L1 inhibitory pathways independently regulate host resistance to Plasmodium-induced acute immune pathology. PLOS Pathog 8:e1002504
     [Google Scholar]
  106. 106.
    Eming SA, Wynn TA, Martin P 2017. Inflammation and metabolism in tissue repair and regeneration. Science 356:1026–30
     [Google Scholar]
  107. 107.
    Cressman DE, Greenbaum LE, DeAngelis RA, Ciliberto G, Furth EE et al. 1996. Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science 274:1379–83
     [Google Scholar]
  108. 108.
    Yamada Y, Kirillova I, Peschon JJ, Fausto N 1997. Initiation of liver growth by tumor necrosis factor: deficient liver regeneration in mice lacking type I tumor necrosis factor receptor. PNAS 94:1441–46
     [Google Scholar]
  109. 109.
    Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y et al. 1986. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 324:73–76
     [Google Scholar]
  110. 110.
    Xu N, Wang SQ, Tan D, Gao Y, Lin G, Xi R 2011. EGFR, Wingless and JAK/STAT signaling cooperatively maintain Drosophila intestinal stem cells. Dev. Biol. 354:31–43
     [Google Scholar]
  111. 111.
    Taniguchi K, Wu LW, Grivennikov SI, de Jong PR, Lian I et al. 2015. A gp130-Src-YAP module links inflammation to epithelial regeneration. Nature 519:57–62
     [Google Scholar]
  112. 112.
    Dumoutier L, Louahed J, Renauld JC 2000. Cloning and characterization of IL-10-related T cell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9. J. Immunol. 164:1814–19
     [Google Scholar]
  113. 113.
    Ahlfors H, Morrison PJ, Duarte JH, Li Y, Biro J et al. 2014. IL-22 fate reporter reveals origin and control of IL-22 production in homeostasis and infection. J. Immunol. 193:4602–13
     [Google Scholar]
  114. 114.
    Mastelic B, do Rosario AP, Veldhoen M, Renauld JC, Jarra W et al. 2012. IL-22 protects against liver pathology and lethality of an experimental blood-stage malaria infection. Front. Immunol. 3:85
     [Google Scholar]
  115. 115.
    Gimblet C, Loesche MA, Carvalho L, Carvalho EM, Grice EA et al. 2015. IL-22 protects against tissue damage during cutaneous leishmaniasis. PLOS ONE 10:e0134698
     [Google Scholar]
  116. 116.
    Guabiraba R, Besnard AG, Marques RE, Maillet I, Fagundes CT et al. 2013. IL-22 modulates IL-17A production and controls inflammation and tissue damage in experimental dengue infection. Eur. J. Immunol. 43:1529–44
     [Google Scholar]
  117. 117.
    Pociask DA, Scheller EV, Mandalapu S, McHugh KJ, Enelow RI et al. 2013. IL-22 is essential for lung epithelial repair following influenza infection. Am. J. Pathol. 182:1286–96
     [Google Scholar]
  118. 118.
    Pickert G, Neufert C, Leppkes M, Zheng Y, Wittkopf N et al. 2009. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J. Exp. Med. 206:1465–72
     [Google Scholar]
  119. 119.
    Xing WW, Zou MJ, Liu S, Xu T, Gao J et al. 2011. Hepatoprotective effects of IL-22 on fulminant hepatic failure induced by d-galactosamine and lipopolysaccharide in mice. Cytokine 56:174–79
     [Google Scholar]
  120. 120.
    Turer EE, Tavares RM, Mortier E, Hitotsumatsu O, Advincula R et al. 2008. Homeostatic MyD88-dependent signals cause lethal inflamMation in the absence of A20. J. Exp. Med. 205:451–64
     [Google Scholar]
  121. 121.
    Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R 2004. Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 118:229–41
     [Google Scholar]
  122. 122.
    Beyer HS, Theologides A 1993. Tumor necrosis factor-alpha is a direct hepatocyte mitogen in the rat. Biochem. Mol. Biol. Int. 29:1–4
     [Google Scholar]
  123. 123.
    Tamura M, Arakaki N, Tsubouchi H, Takada H, Daikuhara Y 1993. Enhancement of human hepatocyte growth factor production by interleukin-1α and -1β and tumor necrosis factor-α by fibroblasts in culture. J. Biol. Chem. 268:8140–45
     [Google Scholar]
  124. 124.
    Black RA, Rauch CT, Kozlosky CJ, Peschon JJ, Slack JL et al. 1997. A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells. Nature 385:729–33
     [Google Scholar]
  125. 125.
    Blaydon DC, Biancheri P, Di WL, Plagnol V, Cabral RM et al. 2011. Inflammatory skin and bowel disease linked to ADAM17 deletion. N. Engl. J. Med. 365:1502–8
     [Google Scholar]
  126. 126.
    Chalaris A, Adam N, Sina C, Rosenstiel P, Lehmann-Koch J et al. 2010. Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice. J. Exp. Med. 207:1617–24
     [Google Scholar]
  127. 127.
    Scheller J, Chalaris A, Garbers C, Rose-John S 2011. ADAM17: a molecular switch to control inflammation and tissue regeneration. Trends Immunol 32:380–87
     [Google Scholar]
  128. 128.
    Jamieson AM, Pasman L, Yu S, Gamradt P, Homer RJ et al. 2013. Role of tissue protection in lethal respiratory viral-bacterial coinfection. Science 340:1230–34
     [Google Scholar]
  129. 129.
    Monticelli LA, Osborne LC, Noti M, Tran SV, Zaiss DMW, Artis D 2015. IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions. PNAS 112:10762–67
     [Google Scholar]
  130. 130.
    Monticelli LA, Sonnenberg GF, Abt MC, Alenghat T, Ziegler CG et al. 2011. Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat. Immunol. 12:1045–54
     [Google Scholar]
  131. 131.
    Arpaia N, Green JA, Moltedo B, Arvey A, Hemmers S et al. 2015. a distinct function of regulatory T cells in tissue protection. Cell 162:1078–89
     [Google Scholar]
  132. 132.
    Burzyn D, Kuswanto W, Kolodin D, Shadrach JL, Cerletti M et al. 2013. A special population of regulatory T cells potentiates muscle repair. Cell 155:1282–95
     [Google Scholar]
  133. 133.
    Schiering C, Krausgruber T, Chomka A, Frohlich A, Adelmann K et al. 2014. The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature 513:564–68
     [Google Scholar]
  134. 134.
    Cardoso V, Chesne J, Ribeiro H, Garcia-Cassani B, Carvalho T et al. 2017. Neuronal regulation of type 2 innate lymphoid cells via neuromedin U. Nature 549:277–81
     [Google Scholar]
  135. 135.
    Ali N, Zirak B, Rodriguez RS, Pauli ML, Truong HA et al. 2017. Regulatory T cells in skin facilitate epithelial stem cell differentiation. Cell 169:1119–29.e11
     [Google Scholar]
  136. 136.
    Dombrowski Y, O'Hagan T, Dittmer M, Penalva R, Mayoral SR et al. 2017. Regulatory T cells promote myelin regeneration in the central nervous system. Nat. Neurosci. 20:674–80
     [Google Scholar]
  137. 137.
    Kuswanto W, Burzyn D, Panduro M, Wang KK, Jang YC et al. 2016. Poor repair of skeletal muscle in aging mice reflects a defect in local, interleukin-33-dependent accumulation of regulatory T cells. Immunity 44:355–67
     [Google Scholar]
  138. 138.
    Zacchigna S, Martinelli V, Moimas S, Colliva A, Anzini M et al. 2018. Paracrine effect of regulatory T cells promotes cardiomyocyte proliferation during pregnancy and after myocardial infarction. Nat. Commun. 9:2432
     [Google Scholar]
  139. 139.
    Hui SP, Sheng DZ, Sugimoto K, Gonzalez-Rajal A, Nakagawa S et al. 2017. Zebrafish regulatory T cells mediate organ-specific regenerative programs. Dev. Cell 43:659–72.e5
     [Google Scholar]
  140. 140.
    Allen JE, Wynn TA 2011. Evolution of Th2 immunity: a rapid repair response to tissue destructive pathogens. PLOS Pathog 7:e1002003
     [Google Scholar]
  141. 141.
    Martinez FO, Helming L, Gordon S 2009. Alternative activation of macrophages: an immunologic functional perspective. Annu. Rev. Immunol. 27:451–83
     [Google Scholar]
  142. 142.
    Bosurgi L, Cao YG, Cabeza-Cabrerizo M, Tucci A, Hughes LD et al. 2017. Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells. Science 356:1072–76
     [Google Scholar]
  143. 143.
    Okabe Y, Medzhitov R 2015. Tissue biology perspective on macrophages. Nat. Immunol. 17:9–17
     [Google Scholar]
  144. 144.
    Eichenfield DZ, Troutman TD, Link VM, Lam MT, Cho H et al. 2016. Tissue damage drives co-localization of NF-κB, Smad3, and Nrf2 to direct Rev-erb sensitive wound repair in mouse macrophages. eLife 5:e13024
     [Google Scholar]
  145. 145.
    Byram JE, von Lichtenberg F 1977. Altered schistosome granuloma formation in nude mice. Am. J. Trop. Med. Hyg. 26:944–56
     [Google Scholar]
  146. 146.
    Pesce JT, Ramalingam TR, Mentink-Kane MM, Wilson MS, El Kasmi KC et al. 2009. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLOS Pathog 5:e1000371
     [Google Scholar]
  147. 147.
    Honda K, Littman DR 2016. The microbiota in adaptive immune homeostasis and disease. Nature 535:75–84
     [Google Scholar]
  148. 148.
    Ayres JS 2016. Cooperative microbial tolerance behaviors in host-microbiota mutualism. Cell 165:1323–31
     [Google Scholar]
  149. 149.
    Schieber AM, Lee YM, Chang MW, Leblanc M, Collins B et al. 2015. Disease tolerance mediated by microbiome E. coli involves inflammasome and IGF-1 signaling. Science 350:558–63
     [Google Scholar]
  150. 150.
    Pan X, Zhou G, Wu J, Bian G, Lu P et al. 2012. Wolbachia induces reactive oxygen species (ROS)-dependent activation of the Toll pathway to control dengue virus in the mosquito Aedes aegypti. . PNAS 109:E23–31
     [Google Scholar]
  151. 151.
    Ha EM, Oh CT, Ryu JH, Bae YS, Kang SW et al. 2005. An antioxidant system required for host protection against gut infection in Drosophila. Dev. . Cell 8:125–32
     [Google Scholar]
  152. 152.
    Jones RM, Desai C, Darby TM, Luo L, Wolfarth AA et al. 2015. Lactobacilli modulate epithelial cytoprotection through the Nrf2 pathway. Cell Rep 12:1217–25
     [Google Scholar]
  153. 153.
    Kremer N, Charif D, Henri H, Gavory F, Wincker P et al. 2012. Influence of Wolbachia on host gene expression in an obligatory symbiosis. BMC Microbiol 12:Suppl. 1S7
     [Google Scholar]
  154. 154.
    Shen Y, Giardino Torchia ML, Lawson GW, Karp CL, Ashwell JD, Mazmanian SK 2012. Outer membrane vesicles of a human commensal mediate immune regulation and disease protection. Cell Host Microbe 12:509–20
     [Google Scholar]
  155. 155.
    Mazmanian SK, Round JL, Kasper DL 2008. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453:620–25
     [Google Scholar]
  156. 156.
    Hickey CA, Kuhn KA, Donermeyer DL, Porter NT, Jin C et al. 2015. Colitogenic Bacteroides thetaiotaomicron antigens access host immune cells in a sulfatase-dependent manner via outer membrane vesicles. Cell Host Microbe 17:672–80
     [Google Scholar]
  157. 157.
    Bloom SM, Bijanki VN, Nava GM, Sun L, Malvin NP et al. 2011. Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease. Cell Host Microbe 9:390–403
     [Google Scholar]
  158. 158.
    Danne C, Ryzhakov G, Martinez-Lopez M, Ilott NE, Franchini F et al. 2017. A large polysaccharide produced by Helicobacter hepaticus induces an anti-inflammatory gene signature in macrophages. Cell Host Microbe 22:733–45.e5
     [Google Scholar]
  159. 159.
    Pickard JM, Maurice CF, Kinnebrew MA, Abt MC, Schenten D et al. 2014. Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness. Nature 514:638–41
     [Google Scholar]
  160. 160.
    Goto Y, Obata T, Kunisawa J, Sato S, Ivanov II et al. 2014. Innate lymphoid cells regulate intestinal epithelial cell glycosylation. Science 345:1254009
     [Google Scholar]
  161. 161.
    Sonnenberg GF, Monticelli LA, Alenghat T, Fung TC, Hutnick NA et al. 2012. Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science 336:1321–25
     [Google Scholar]
  162. 162.
    Pham TA, Clare S, Goulding D, Arasteh JM, Stares MD et al. 2014. Epithelial IL-22RA1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen. Cell Host Microbe 16:504–16
     [Google Scholar]
  163. 163.
    Ng KM, Ferreyra JA, Higginbottom SK, Lynch JB, Kashyap PC et al. 2013. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature 502:96–99
     [Google Scholar]
  164. 164.
    Kamada N, Kim YG, Sham HP, Vallance BA, Puente JL et al. 2012. Regulated virulence controls the ability of a pathogen to compete with the gut microbiota. Science 336:1325–29
     [Google Scholar]
  165. 165.
    Pacheco AR, Curtis MM, Ritchie JM, Munera D, Waldor MK et al. 2012. Fucose sensing regulates bacterial intestinal colonization. Nature 492:113–17
     [Google Scholar]
  166. 166.
    Lawhon SD, Maurer R, Suyemoto M, Altier C 2002. Intestinal short-chain fatty acids alter Salmonella typhimurium invasion gene expression and virulence through BarA/SirA. Mol. Microbiol. 46:1451–64
     [Google Scholar]
  167. 167.
    Jacobson A, Lam L, Rajendram M, Tamburini F, Honeycutt J et al. 2018. A gut commensal-produced metabolite mediates colonization resistance to Salmonella infection. Cell Host Microbe 24:2296–307.e7
     [Google Scholar]
  168. 168.
    Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T et al. 2011. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331:337–41
     [Google Scholar]
  169. 169.
    Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA et al. 2013. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341:569–73
     [Google Scholar]
  170. 170.
    Chang PV, Hao L, Offermanns S, Medzhitov R 2014. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. PNAS 111:2247–52
     [Google Scholar]
  171. 171.
    Obata T, Goto Y, Kunisawa J, Sato S, Sakamoto M et al. 2010. Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis. PNAS 107:7419–24
     [Google Scholar]
  172. 172.
    Fung TC, Bessman NJ, Hepworth MR, Kumar N, Shibata N et al. 2016. Lymphoid-tissue-resident commensal bacteria promote members of the IL-10 cytokine family to establish mutualism. Immunity 44:634–46
     [Google Scholar]
  173. 173.
    Bandyopadhaya A, Tsurumi A, Maura D, Jeffrey KL, Rahme LG 2016. A quorum-sensing signal promotes host tolerance training through HDAC1-mediated epigenetic reprogramming. Nat. Microbiol. 1:16174
     [Google Scholar]
  174. 174.
    Roberts HC, Hardie LJ, Chappell LH, Mercer JG 1999. Parasite-induced anorexia: leptin, insulin and corticosterone responses to infection with the nematode. Nippostrongylus brasiliensis. Parasitology 118:Part 1117–23
     [Google Scholar]
  175. 175.
    Palmer LD, Skaar EP 2016. Transition metals and virulence in bacteria. Annu. Rev. Genet. 50:67–91
     [Google Scholar]
  176. 176.
    Weiss G, Goodnough LT 2005. Anemia of chronic disease. N. Engl. J. Med. 352:1011–23
     [Google Scholar]
  177. 177.
    Camaschella C 2015. Iron-deficiency anemia. N. Engl. J. Med. 373:485–86
     [Google Scholar]
  178. 178.
    Muckenthaler MU, Rivella S, Hentze MW, Galy B 2017. A red carpet for iron metabolism. Cell 168:344–61
     [Google Scholar]
  179. 179.
    Andreini C, Banci L, Bertini I, Rosato A 2006. Zinc through the three domains of life. J. Proteome Res. 5:3173–78
     [Google Scholar]
  180. 180.
    Kambe T, Tsuji T, Hashimoto A, Itsumura N 2015. The physiological, biochemical, and molecular roles of zinc transporters in zinc homeostasis and metabolism. Physiol. Rev. 95:749–84
     [Google Scholar]
  181. 181.
    Hood MI, Skaar EP 2012. Nutritional immunity: transition metals at the pathogen-host interface. Nat. Rev. Microbiol. 10:525–37
     [Google Scholar]
  182. 182.
    Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR et al. 2008. Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319:962–65
     [Google Scholar]
  183. 183.
    Urban CF, Ermert D, Schmid M, Abu-Abed U, Goosmann C et al. 2009. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. . PLOS Pathog 5:e1000639
     [Google Scholar]
  184. 184.
    Subramanian Vignesh K, Landero Figueroa JA, Porollo A, Caruso JA, Deepe GS Jr 2013. Granulocyte macrophage-colony stimulating factor induced Zn sequestration enhances macrophage superoxide and limits intracellular pathogen survival. Immunity 39:697–710
     [Google Scholar]
  185. 185.
    Roohani N, Hurrell R, Kelishadi R, Schulin R 2013. Zinc and its importance for human health: an integrative review. J. Res. Med. Sci. 18:144–57
     [Google Scholar]
  186. 186.
    Bobat R, Coovadia H, Stephen C, Naidoo KL, McKerrow N et al. 2005. Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial. Lancet 366:1862–67
     [Google Scholar]
  187. 187.
    Hiroshima Y, Hsu K, Tedla N, Wong SW, Chow S et al. 2017. S100A8/A9 and S100A9 reduce acute lung injury. Immunol. Cell Biol. 95:461–72
     [Google Scholar]
  188. 188.
    Ferreira FBD, Dos Santos C, Bruxel MA, Nunes EA, Spiller F, Rafacho A 2017. Glucose homeostasis in two degrees of sepsis lethality induced by caecum ligation and puncture in mice. Int. J. Exp. Pathol. 98:329–40
     [Google Scholar]
  189. 189.
    Mancio-Silva L, Slavic K, Grilo Ruivo MT, Grosso AR, Modrzynska KK et al. 2017. Nutrient sensing modulates malaria parasite virulence. Nature 547:213–16
     [Google Scholar]
  190. 190.
    Wang A, Huen SC, Luan HA, Baker K, Rinder H et al. 2018. Glucose metabolism mediates disease tolerance in cerebral malaria. PNAS 115:11042–47
     [Google Scholar]
  191. 191.
    Cumnock K, Gupta AS, Lissner M, Chevee V, Davis NM, Schneider DS 2018. Host energy source is important for disease tolerance to malaria. Curr. Biol. 28:1635–42.e3
     [Google Scholar]
  192. 192.
    Sanchez KK, Chen GY, Schieber AMP, Redford SE, Shokhirev MN et al. 2018. Cooperative metabolic adaptations in the host can favor asymptomatic infection and select for attenuated virulence in an enteric pathogen. Cell 175:146–58.e15
     [Google Scholar]
  193. 193.
    Murray PJ 2016. Amino acid auxotrophy as a system of immunological control nodes. Nat. Immunol. 17:132–39
     [Google Scholar]
  194. 194.
    Murray HW, Szuro-Sudol A, Wellner D, Oca MJ, Granger AM et al. 1989. Role of tryptophan degradation in respiratory burst-independent antimicrobial activity of gamma interferon-stimulated human macrophages. Infect. Immun. 57:845–49
     [Google Scholar]
  195. 195.
    Mellor AL, Munn DH 2004. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat. Rev. Immunol. 4:762–74
     [Google Scholar]
  196. 196.
    Soares MP, Bach FH 2007. Heme oxygenase-1 in organ transplantation. Front. Biosci. 12:4932–45
     [Google Scholar]
  197. 197.
    Soares MP, Lin Y, Sato K, Stuhlmeier KM, Bach FH 1999. Accommodation. Immunol. Today 20:434–37
     [Google Scholar]
  198. 198.
    Soares MP, Lin Y, Anrather J, Csizmadia E, Takigami K et al. 1998. Expression of heme oxygenase-1 can determine cardiac xenograft survival. Nat. Med. 4:1073–77
     [Google Scholar]
  199. 199.
    Engin F, Yermalovich A, Nguyen T, Hummasti S, Fu W et al. 2013. Restoration of the unfolded protein response in pancreatic beta cells protects mice against type 1 diabetes. Sci. Transl. Med. 5:211ra156
     [Google Scholar]
  200. 200.
    Huang SH, Chu CH, Yu JC, Chuang WC, Lin GJ et al. 2010. Transgenic expression of haem oxygenase-1 in pancreatic beta cells protects non-obese mice used as a model of diabetes from autoimmune destruction and prolongs graft survival following islet transplantation. Diabetologia 53:2389–400
     [Google Scholar]
  201. 201.
    Moller DE, Kaufman KD 2005. Metabolic syndrome: a clinical and molecular perspective. Annu. Rev. Med. 56:45–62
     [Google Scholar]
  202. 202.
    Sundstrom J, Riserus U, Byberg L, Zethelius B, Lithell H, Lind L 2006. Clinical value of the metabolic syndrome for long term prediction of total and cardiovascular mortality: prospective, population based cohort study. BMJ 332:878–82
     [Google Scholar]
  203. 203.
    Uruno A, Furusawa Y, Yagishita Y, Fukutomi T, Muramatsu H et al. 2013. The Keap1-Nrf2 system prevents onset of diabetes mellitus. Mol. Cell Biol. 33:2996–3010
     [Google Scholar]
  204. 204.
    Cheng K, Ho K, Stokes R, Scott C, Lau SM et al. 2010. Hypoxia-inducible factor-1α regulates β cell function in mouse and human islets. J. Clin. Investig. 120:2171–83
     [Google Scholar]
  205. 205.
    Jais A, Einwallner E, Sharif O, Gossens K, Lu TT et al. 2014. Heme oxygenase-1 drives metaflammation and insulin resistance in mouse and man. Cell 158:25–40
     [Google Scholar]
  206. 206.
    Freigang S, Ampenberger F, Spohn G, Heer S, Shamshiev AT et al. 2011. Nrf2 is essential for cholesterol crystal-induced inflammasome activation and exacerbation of atherosclerosis. Eur. J. Immunol. 41:2040–51
     [Google Scholar]
  207. 207.
    Stearns SC, Medzhitov R 2015. Evolutionary Medicine Sunderland, MA: Oxford Univ. Press
  208. 208.
    Hanahan D, Weinberg RA 2011. Hallmarks of cancer: the next generation. Cell 144:646–74
     [Google Scholar]
  209. 209.
    Palucka AK, Coussens LM 2016. The basis of oncoimmunology. Cell 164:1233–47
     [Google Scholar]
  210. 210.
    Dillman AR, Schneider DS 2015. Defining resistance and tolerance to cancer. Cell Rep 13:884–87
     [Google Scholar]
  211. 211.
    Menegon S, Columbano A, Giordano S 2016. The dual roles of NRF2 in cancer. Trends Mol. Med. 22:578–93
     [Google Scholar]
  212. 212.
    Remo A, Simeone I, Pancione M, Parcesepe P, Finetti P et al. 2015. Systems biology analysis reveals NFAT5 as a novel biomarker and master regulator of inflammatory breast cancer. J. Transl. Med. 13:138
     [Google Scholar]
  213. 213.
    Vousden KH, Lane DP 2007. p53 in health and disease. Nat. Rev. Mol. Cell Biol. 8:275–83
     [Google Scholar]
  214. 214.
    Grivennikov SI, Greten FR, Karin M 2010. Immunity, inflammation, and cancer. Cell 140:883–99
     [Google Scholar]
  215. 215.
    Argiles JM, Busquets S, Stemmler B, Lopez-Soriano FJ 2014. Cancer cachexia: understanding the molecular basis. Nat. Rev. Cancer 14:754–62
     [Google Scholar]
  216. 216.
    Warburg O 1956. On the origin of cancer cells. Science 123:309–14
     [Google Scholar]
  217. 217.
    Cooper DN, Krawczak M, Polychronakos C, Tyler-Smith C, Kehrer-Sawatzki H 2013. Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease. Hum. Genet. 132:1077–130
     [Google Scholar]
  218. 218.
    Blekhman R, Man O, Herrmann L, Boyko AR, Indap A et al. 2008. Natural selection on genes that underlie human disease susceptibility. Curr. Biol. 18:883–89
     [Google Scholar]
  219. 219.
    Kato GJ, Piel FB, Reid CD, Gaston MH, Ohene-Frempong K et al. 2018. Sickle cell disease. Nat. Rev. Dis. Primers 4:18010
     [Google Scholar]
  220. 220.
    Bunn HF 2013. The triumph of good over evil: protection by the sickle gene against malaria. Blood 121:20–25
     [Google Scholar]
  221. 221.
    Zhu X, Xi C, Thomas B, Pace BS 2018. Loss of NRF2 function exacerbates the pathophysiology of sickle cell disease in a transgenic mouse model. Blood 131:558–62
     [Google Scholar]
  222. 222.
    Belcher JD, Vineyard JV, Bruzzone CM, Chen C, Beckman JD et al. 2010. Heme oxygenase-1 gene delivery by Sleeping Beauty inhibits vascular stasis in a murine model of sickle cell disease. J. Mol. Med. 88:665–75
     [Google Scholar]
  223. 223.
    Schneider DS 2011. Tracing personalized health curves during infections. PLOS Biol 9:e1001158
     [Google Scholar]
  224. 224.
    Han H, Cho JW, Lee S, Yun A, Kim H et al. 2018. TRRUST v2: an expanded reference database of human and mouse transcriptional regulatory interactions. Nucleic Acids Res 46:D380–86
     [Google Scholar]
  225. 225.
    Huang da W, Sherman BT, Lempicki RA 2009. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4:44–57
     [Google Scholar]
  226. 226.
    Shevach EM 2009. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity 30:636–45
     [Google Scholar]
  227. 227.
    De Vadder F, Kovatcheva-Datchary P, Goncalves D, Vinera J, Zitoun C et al. 2014. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156:84–96
     [Google Scholar]
  228. 228.
    Soty M, Penhoat A, Amigo-Correig M, Vinera J, Sardella A et al. 2015. A gut-brain neural circuit controlled by intestinal gluconeogenesis is crucial in metabolic health. Mol. Metab. 4:106–17
     [Google Scholar]
  229. 229.
    De Vadder F, Kovatcheva-Datchary P, Zitoun C, Duchampt A, Backhed F, Mithieux G 2016. Microbiota-produced succinate improves glucose homeostasis via intestinal gluconeogenesis. Cell Metab 24:151–57
     [Google Scholar]
  230. 230.
    Soty M, Gautier-Stein A, Rajas F, Mithieux G 2017. Gut-brain glucose signaling in energy homeostasis. Cell Metab 25:1231–42
     [Google Scholar]
  231. 231.
    Veiga-Parga T, Suryawanshi A, Rouse BT 2011. Controlling viral immuno-inflammatory lesions by modulating aryl hydrocarbon receptor signaling. PLOS Pathog 7:e1002427
     [Google Scholar]
  232. 232.
    Trompette A, Gollwitzer ES, Pattaroni C, Lopez-Mejia IC, Riva E et al. 2018. Dietary fiber confers protection against flu by shaping Ly6c− patrolling monocyte hematopoiesis and CD8+ T cell metabolism. Immunity 48:992–1005.e8
     [Google Scholar]
  233. 233.
    Thimmulappa RK, Lee H, Rangasamy T, Reddy SP, Yamamoto M et al. 2006. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J. Clin. Investig. 116:984–95
     [Google Scholar]
  234. 234.
    Mita M, Satoh M, Shimada A, Okajima M, Azuma S et al. 2008. Metallothionein is a crucial protective factor against Helicobacter pylori-induced gastric erosive lesions in a mouse model. Am. J. Physiol. Gastrointest. Liver Physiol. 294:G877–84
     [Google Scholar]
  235. 235.
    Thompson AA, Dickinson RS, Murphy F, Thomson JP, Marriott HM et al. 2017. Hypoxia determines survival outcomes of bacterial infection through HIF-1α dependent re-programming of leukocyte metabolism. Sci. Immunol. 2:eaal2861
     [Google Scholar]
  236. 236.
    Lee HH, Sanada S, An SM, Ye BJ, Lee JH et al. 2016. LPS-induced NFκB enhanceosome requires TonEBP/NFAT5 without DNA binding. Sci. Rep. 6:24921
     [Google Scholar]
  237. 237.
    Murapa P, Ward MR, Gandhapudi SK, Woodward JG, D'Orazio SE 2011. Heat shock factor 1 protects mice from rapid death during Listeria monocytogenes infection by regulating expression of tumor necrosis factor alpha during fever. Infect. Immun. 79:177–84
     [Google Scholar]
  238. 238.
    Trakala M, Arias CF, Garcia MI, Moreno-Ortiz MC, Tsilingiri K et al. 2009. Regulation of macrophage activation and septic shock susceptibility via p21(WAF1/CIP1). Eur. J. Immunol. 39:810–19
     [Google Scholar]
  239. 239.
    Liu G, Park YJ, Tsuruta Y, Lorne E, Abraham E 2009. p53 attenuates lipopolysaccharide-induced NF-κB activation and acute lung injury. J. Immunol. 182:5063–71
     [Google Scholar]
  240. 240.
    Madenspacher JH, Azzam KM, Gowdy KM, Malcolm KC, Nick JA et al. 2013. p53 integrates host defense and cell fate during bacterial pneumonia. J. Exp. Med. 210:891–904
     [Google Scholar]
  241. 241.
    Temiz-Resitoglu M, Kucukkavruk SP, Guden DS, Cecen P, Sari AN et al. 2017. Activation of mTOR/IκB-α/NF-κB pathway contributes to LPS-induced hypotension and inflammation in rats. Eur. J. Pharmacol. 802:7–19
     [Google Scholar]
  242. 242.
    Hu Y, Lou J, Mao YY, Lai TW, Liu LY et al. 2016. Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury. Autophagy 12:2286–99
     [Google Scholar]
  243. 243.
    Liu H, Huang L, Bradley J, Liu K, Bardhan K et al. 2014. GCN2-dependent metabolic stress is essential for endotoxemic cytokine induction and pathology. Mol. Cell Biol. 34:428–38
     [Google Scholar]
  244. 244.
    Oishi Y, Spann NJ, Link VM, Muse ED, Strid T et al. 2017. SREBP1 contributes to resolution of pro-inflammatory TLR4 signaling by reprogramming fatty acid metabolism. Cell Metab 25:412–27
     [Google Scholar]
  245. 245.
    Figueiredo N, Chora A, Raquel H, Pejanovic N, Pereira P et al. 2013. Anthracyclines induce DNA damage response-mediated protection against severe sepsis. Immunity 39:874–84
     [Google Scholar]
  246. 246.
    Qian L, Zhao Y, Guo L, Li S, Wu X 2017. Activating transcription factor 3 (ATF3) protects against lipopolysaccharide-induced acute lung injury via inhibiting the expression of TL1A. J. Cell Physiol. 232:3727–34
     [Google Scholar]
  247. 247.
    Gao R, Chen J, Hu Y, Li Z, Wang S et al. 2014. Sirt1 deletion leads to enhanced inflammation and aggravates endotoxin-induced acute kidney injury. PLOS ONE 9:e98909
     [Google Scholar]
  248. 248.
    Wan X, Wen JJ, Koo SJ, Liang LY, Garg NJ 2016. SIRT1-PGC1α-NFκB pathway of oxidative and inflammatory stress during Trypanosoma cruzi infection: benefits of SIRT1-targeted therapy in improving heart function in Chagas disease. PLOS Pathog 12:e1005954
     [Google Scholar]
  249. 249.
    Courtine E, Pene F, Cagnard N, Toubiana J, Fitting C et al. 2011. Critical role of cRel subunit of NF-κB in sepsis survival. Infect. Immun. 79:1848–54
     [Google Scholar]
  250. 250.
    Lachance C, Segura M, Gerber PP, Xu J, Gottschalk M 2013. Toll-like receptor 2-independent host innate immune response against an epidemic strain of Streptococcus suis that causes a toxic shock-like syndrome in humans. PLOS ONE 8:e65031
     [Google Scholar]
  251. 251.
    Kirman J, McCoy K, Hook S, Prout M, Delahunt B et al. 1999. CTLA-4 blockade enhances the immune response induced by mycobacterial infection but does not lead to increased protection. Infect. Immun. 67:3786–92
     [Google Scholar]
  252. 252.
    Huang X, Chen Y, Chung CS, Yuan Z, Monaghan SF et al. 2014. Identification of B7-H1 as a novel mediator of the innate immune/proinflammatory response as well as a possible myeloid cell prognostic biomarker in sepsis. J. Immunol. 192:1091–99
     [Google Scholar]
  253. 253.
    Castiglia V, Piersigilli A, Ebner F, Janos M, Goldmann O et al. 2016. Type I interferon signaling prevents IL-1β-driven lethal systemic hyperinflammation during invasive bacterial infection of soft tissue. Cell Host Microbe 19:375–87
     [Google Scholar]
  254. 254.
    Zheng Y, Valdez PA, Danilenko DM, Hu Y, Sa SM et al. 2008. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat. Med. 14:282–89
     [Google Scholar]
  255. 255.
    Maurer K, Reyes-Robles T, Alonzo F, Durbin J, Torres VJ, Cadwell K 2015. Autophagy mediates tolerance to Staphylococcus aureus alpha-toxin. Cell Host Microbe 17:429–40
     [Google Scholar]
  256. 256.
    Inoshima I, Inoshima N, Wilke GA, Powers ME, Frank KM et al. 2011. A Staphylococcus aureus pore-forming toxin subverts the activity of ADAM10 to cause lethal infection in mice. Nat. Med. 17:1310–14
     [Google Scholar]
  257. 257.
    Coban C, Ishii KJ, Uematsu S, Arisue N, Sato S et al. 2007. Pathological role of Toll-like receptor signaling in cerebral malaria. Int. Immunol. 19:67–79
     [Google Scholar]
  258. 258.
    Villegas-Mendez A, de Souza JB, Murungi L, Hafalla JC, Shaw TN et al. 2011. Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-γ during Plasmodium berghei ANKA infection. J. Immunol. 187:2885–97
     [Google Scholar]
  259. 259.
    Engwerda CR, Mynott TL, Sawhney S, De Souza JB, Bickle QD, Kaye PM 2002. Locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha, is the principle mediator of murine cerebral malaria. J. Exp. Med. 195:1371–77
     [Google Scholar]
  260. 260.
    Palomo J, Reverchon F, Piotet J, Besnard AG, Couturier-Maillard A et al. 2015. Critical role of IL-33 receptor ST2 in experimental cerebral malaria development. Eur. J. Immunol. 45:1354–65
     [Google Scholar]
  261. 261.
    Wunderlich CM, Delic D, Behnke K, Meryk A, Strohle P et al. 2012. Cutting edge: Inhibition of IL-6 trans-signaling protects from malaria-induced lethality in mice. J. Immunol. 188:4141–44
     [Google Scholar]
  262. 262.
    Schofield L, Hewitt MC, Evans K, Siomos MA, Seeberger PH 2002. Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria. Nature 418:785–89
     [Google Scholar]
  263. 263.
    Briquet S, Lawson-Hogban N, Boisson B, Soares MP, Peronet R et al. 2015. Disruption of parasite hmgb2 gene attenuates Plasmodium berghei ANKA pathogenicity. Infect. Immun. 83:2771–84
     [Google Scholar]
  264. 264.
    Majer O, Bourgeois C, Zwolanek F, Lassnig C, Kerjaschki D et al. 2012. Type I interferons promote fatal immunopathology by regulating inflammatory monocytes and neutrophils during Candida infections. PLOS Pathog 8:e1002811
     [Google Scholar]
  265. 265.
    Huang J, Meng S, Hong S, Lin X, Jin W, Dong C 2016. IL-17C is required for lethal inflammation during systemic fungal infection. Cell Mol. Immunol. 13:474–83
     [Google Scholar]
  266. 266.
    Tsitsigiannis DI, Bok JW, Andes D, Nielsen KF, Frisvad JC, Keller NP 2005. Aspergillus cyclooxygenase-like enzymes are associated with prostaglandin production and virulence. Infect. Immun. 73:4548–59
     [Google Scholar]
  267. 267.
    Scalfone LK, Nel HJ, Gagliardo LF, Cameron JL, Al-Shokri S et al. 2013. Participation of MyD88 and interleukin-33 as innate drivers of Th2 immunity to Trichinella spiralis. Infect. . Immun 81:1354–63
     [Google Scholar]
  268. 268.
    Herbert DR, Holscher C, Mohrs M, Arendse B, Schwegmann A et al. 2004. Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology. Immunity 20:623–35
     [Google Scholar]
/content/journals/10.1146/annurev-immunol-042718-041739
Loading
Disease Tolerance as an Inherent Component of Immunity
Annual Review of Immunology 37, 405 (2019); https://doi.org/10.1146/annurev-immunol-042718-041739
/content/journals/10.1146/annurev-immunol-042718-041739
/content/journals/10.1146/annurev-immunol-042718-041739
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error