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Abstract

Immunity to infection has been extensively studied in humans and mice bearing naturally occurring or experimentally introduced germline mutations. Mouse studies are sometimes neglected by human immunologists, on the basis that mice are not humans and the infections studied are experimental and not natural. Conversely, human studies are sometimes neglected by mouse immunologists, on the basis of the uncontrolled conditions of study and small numbers of patients. However, both sides would agree that the infectious phenotypes of patients with inborn errors of immunity often differ from those of the corresponding mutant mice. Why is that? We argue that this important question is best addressed by revisiting and reinterpreting the findings of both mouse and human studies from a genetic perspective. Greater caution is required for reverse-genetics studies than for forward-genetics studies, but genetic analysis is sufficiently strong to define the studies likely to stand the test of time. Genetically robust mouse and human studies can provide invaluable complementary insights into the mechanisms of immunity to infection common and specific to these two species.

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2023-04-26
2024-10-06
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Literature Cited

  1. 1.
    Casanova JL, Su HCCOVID Hum. Genet. Effort 2020. A global effort to define the human genetics of protective immunity to SARS-CoV-2 infection. Cell 181:1194–99
    [Google Scholar]
  2. 2.
    Zhang Q, Bastard P, COVID Hum. Genet. Effort, Cobat A, Casanova JL 2022. Human genetic and immunological determinants of critical COVID-19 pneumonia. Nature 603:587–98
    [Google Scholar]
  3. 3.
    Haller O, Arnheiter H, Pavlovic J, Staeheli P. 2018. The discovery of the antiviral resistance gene Mx: a story of great ideas, great failures, and some success. Annu. Rev. Virol. 5:33–51
    [Google Scholar]
  4. 4.
    Staeheli P, Haller O, Boll W, Lindenmann J, Weissmann C. 1986. Mx protein: constitutive expression in 3T3 cells transformed with cloned Mx cDNA confers selective resistance to influenza virus. Cell 44:147–58
    [Google Scholar]
  5. 5.
    Doetschman T, Gregg RG, Maeda N, Hooper ML, Melton DW et al. 1987. Targetted correction of a mutant HPRT gene in mouse embryonic stem cells. Nature 330:576–78
    [Google Scholar]
  6. 6.
    Thomas KR, Capecchi MR. 1987. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51:503–12
    [Google Scholar]
  7. 7.
    Quintana-Murci L, Alcaïs A, Abel L, Casanova JL. 2007. Immunology in natura: clinical, epidemiological and evolutionary genetics of infectious diseases. Nat. Immunol. 8:1165–71
    [Google Scholar]
  8. 8.
    Pulendran B, Davis MM. 2020. The science and medicine of human immunology. Science 369:eaay4014
    [Google Scholar]
  9. 9.
    Hayday AC, Peakman M. 2008. The habitual, diverse and surmountable obstacles to human immunology research. Nat. Immunol. 9:575–80
    [Google Scholar]
  10. 10.
    Davis MM, Brodin P. 2018. Rebooting human immunology. Annu. Rev. Immunol. 36:843–64
    [Google Scholar]
  11. 11.
    Davis MM. 2008. A prescription for human immunology. Immunity 29:835–38
    [Google Scholar]
  12. 12.
    Casanova JL, Abel L. 2004. The human model: a genetic dissection of immunity to infection in natural conditions. Nat. Rev. Immunol. 4:55–66
    [Google Scholar]
  13. 13.
    White R, Caskey CT. 1988. The human as an experimental system in molecular genetics. Science 240:48581483–88
    [Google Scholar]
  14. 14.
    Medetgul-Ernar K, Davis MM. 2022. Standing on the shoulders of mice. Immunity 55:81343–53
    [Google Scholar]
  15. 15.
    Casanova JL, Abel L. 2002. Genetic dissection of immunity to mycobacteria: the human model. Annu. Rev. Immunol. 20:581–620
    [Google Scholar]
  16. 16.
    Casanova J-L, Nathan CF, Nussenzweig MC. 2016. Human studies at JEM: immunology and beyond. J. Exp. Med. 213:467–68
    [Google Scholar]
  17. 17.
    Bonthron DT, Markham AF, Ginsburg D, Orkin SH. 1985. Identification of a point mutation in the adenosine deaminase gene responsible for immunodeficiency. J. Clin. Investig. 76:894–97
    [Google Scholar]
  18. 18.
    Lutz W. 1946. A propos de l'epidermodysplasie verruciforme. Dermatologica 92:30–43
    [Google Scholar]
  19. 19.
    Tangye SG, Al-Herz W, Bousfiha A, Chatila T, Cunningham-Rundles C et al. 2020. Human inborn errors of immunity: 2019 update on the classification from the International Union of Immunological Societies Expert Committee. J. Clin. Immunol. 40:24–64. Erratum 2020. J. Clin. Immunol. 40:65
    [Google Scholar]
  20. 20.
    Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL et al. 2021. The ever-increasing array of novel inborn errors of immunity: an interim update by the IUIS committee. J. Clin. Immunol. 41:666–79
    [Google Scholar]
  21. 21.
    Bousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F et al. 2020. Human inborn errors of immunity: 2019 update of the IUIS phenotypical classification. J. Clin. Immunol. 40:66–81
    [Google Scholar]
  22. 22.
    Beura LK, Hamilton SE, Bi K, Schenkel JM, Odumade OA et al. 2016. Normalizing the environment recapitulates adult human immune traits in laboratory mice. Nature 532:512–16
    [Google Scholar]
  23. 23.
    Masopust D, Sivula CP, Jameson SC. 2017. Of mice, dirty mice, and men: using mice to understand human immunology. J. Immunol. 199:383–88
    [Google Scholar]
  24. 24.
    Mestas J, Hughes CC. 2004. Of mice and not men: differences between mouse and human immunology. J. Immunol. 172:2731–38
    [Google Scholar]
  25. 25.
    Sellers RS. 2017. Translating mouse models. Toxicol. Pathol. 45:134–45
    [Google Scholar]
  26. 26.
    Tao L, Reese TA. 2017. Making mouse models that reflect human immune responses. Trends Immunol. 38:181–93
    [Google Scholar]
  27. 27.
    Paludan SR, Mogensen TH, Pradeu T, Masters SL. 2020. Constitutive immune mechanisms: mediators of host defence and immune regulation. Nat. Rev. Immunol. 21:137–50
    [Google Scholar]
  28. 28.
    Randow F, MacMicking JD, James LC. 2013. Cellular self-defense: how cell-autonomous immunity protects against pathogens. Science 340:701–6
    [Google Scholar]
  29. 29.
    Zhang SY, Jouanguy E, Zhang Q, Abel L, Puel A, Casanova JL. 2019. Human inborn errors of immunity to infection affecting cells other than leukocytes: from the immune system to the whole organism. Curr. Opin. Immunol. 59:88–100
    [Google Scholar]
  30. 30.
    Gaudet RG, Zhu S, Halder A, Kim BH, Bradfield CJ et al. 2021. A human apolipoprotein L with detergent-like activity kills intracellular pathogens. Science 373:eabf8113
    [Google Scholar]
  31. 31.
    Nathan C. 2021. Rethinking immunology. Science 373:276–77
    [Google Scholar]
  32. 32.
    Casanova JL, Abel L. 2021. Mechanisms of viral inflammation and disease in humans. Science 374:65711080–86
    [Google Scholar]
  33. 33.
    Crowther MD, Sewell AK. 2021. The burgeoning role of MR1-restricted T-cells in infection, cancer and autoimmune disease. Curr. Opin. Immunol. 69:10–17
    [Google Scholar]
  34. 34.
    Papalexi E, Satija R. 2018. Single-cell RNA sequencing to explore immune cell heterogeneity. Nat. Rev. Immunol. 18:35–45
    [Google Scholar]
  35. 35.
    de Jong SJ, Créquer A, Matos I, Hum D, Gunasekharan V et al. 2018. The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses. J. Exp. Med. 215:2289–310
    [Google Scholar]
  36. 36.
    Spurgeon ME, Lambert PF. 2020. Mus musculus papillomavirus 1: a new frontier in animal models of papillomavirus pathogenesis. J. Virol. 94:e00002–20
    [Google Scholar]
  37. 37.
    von Bernuth H, Picard C, Puel A, Casanova JL. 2012. Experimental and natural infections in MyD88- and IRAK-4-deficient mice and humans. Eur. J. Immunol. 42:3126–35
    [Google Scholar]
  38. 38.
    Casanova J-L, Abel L, Quintana-Murci L 2011. Human TLRs and IL-1Rs in host defense: natural insights from evolutionary, epidemiological, and clinical genetics. Annu. Rev. Immunol. 29:447–91
    [Google Scholar]
  39. 39.
    Yang R, Mele F, Worley L, Langlais D, Rosain J et al. 2020. Human T-bet governs innate and innate-like adaptive IFN-γ immunity against mycobacteria. Cell 183:1826–47
    [Google Scholar]
  40. 40.
    Pöyhönen L, Bustamante J, Casanova J-L, Jouanguy E, Zhang Q 2019. Life-threatening infections due to live-attenuated vaccines: early manifestations of inborn errors of immunity. J. Clin. Immunol. 39:376–90
    [Google Scholar]
  41. 41.
    Yeung F, Chen Y-H, Lin J-D, Leung JM, McCauley C et al. 2020. Altered immunity of laboratory mice in the natural environment is associated with fungal colonization. Cell Host Microbe 27:809–22
    [Google Scholar]
  42. 42.
    Ramanan D, Tang MS, Bowcutt R, Loke P, Cadwell K. 2014. Bacterial sensor Nod2 prevents inflammation of the small intestine by restricting the expansion of the commensal Bacteroides vulgatus. Immunity 41:311–24
    [Google Scholar]
  43. 43.
    Keubler LM, Buettner M, Häger C, Bleich A. 2015. A multihit model: colitis lessons from the interleukin-10-deficient mouse. Inflamm. Bowel Dis. 21:1967–75
    [Google Scholar]
  44. 44.
    Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T et al. 2009. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:485–98
    [Google Scholar]
  45. 45.
    Iliev ID, Cadwell K. 2021. Effects of intestinal fungi and viruses on immune responses and inflammatory bowel diseases. Gastroenterology 160:1050–66
    [Google Scholar]
  46. 46.
    Cadwell K, Patel KK, Maloney NS, Liu T-C, Ng ACY et al. 2010. Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine. Cell 141:1135–45
    [Google Scholar]
  47. 47.
    Boehm T, Hirano M, Holland SJ, Das S, Schorpp M, Cooper MD. 2018. Evolution of alternative adaptive immune systems in vertebrates. Annu. Rev. Immunol. 36:19–42
    [Google Scholar]
  48. 48.
    Casanova JL, Abel L. 2015. Disentangling inborn and acquired immunity in human twins. Cell 160:13–15
    [Google Scholar]
  49. 49.
    Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJ et al. 2015. Variation in the human immune system is largely driven by non-heritable influences. Cell 160:37–47
    [Google Scholar]
  50. 50.
    Puelma Touzel M, Walczak AM, Mora T, Davenport MP. 2020. Inferring the immune response from repertoire sequencing. PLOS Comput. Biol. 16:e1007873
    [Google Scholar]
  51. 51.
    Davenport MP, Smith NL, Rudd BD. 2020. Building a T cell compartment: how immune cell development shapes function. Nat. Rev. Immunol. 20:499–506
    [Google Scholar]
  52. 52.
    Rausell A, Luo Y, Lopez M, Seeleuthner Y, Rapaport F et al. 2020. Common homozygosity for predicted loss-of-function variants reveals both redundant and advantageous effects of dispensable human genes. PNAS 117:13626–36
    [Google Scholar]
  53. 53.
    Quintana-Murci L. 2019. Human immunology through the lens of evolutionary genetics. Cell 177:184–99
    [Google Scholar]
  54. 54.
    Laval G, Peyrégne S, Zidane N, Harmant C, Renaud F et al. 2019. Recent adaptive acquisition by African rainforest hunter-gatherers of the late Pleistocene sickle-cell mutation suggests past differences in malaria exposure. Am. J. Hum. Genet. 104:553–61
    [Google Scholar]
  55. 55.
    Kanjee U, Grüring C, Babar P, Meyers A, Dash R et al. 2021. Plasmodium vivax strains use alternative pathways for invasion. J. Infect. Dis. 223:101817–21
    [Google Scholar]
  56. 56.
    Malone KM, Gordon SV. 2017. Mycobacterium tuberculosis complex members adapted to wild and domestic animals. Adv. Exp. Med. Biol. 1019:135–54
    [Google Scholar]
  57. 57.
    Klingel K, Stephan S, Sauter M, Zell R, McManus BM et al. 1996. Pathogenesis of murine enterovirus myocarditis: virus dissemination and immune cell targets. J. Virol. 70:8888–95
    [Google Scholar]
  58. 58.
    Feuer R, Mena I, Pagarigan RR, Harkins S, Hassett DE, Whitton JL. 2003. Coxsackievirus B3 and the neonatal CNS: the roles of stem cells, developing neurons, and apoptosis in infection, viral dissemination, and disease. Am. J. Pathol. 163:1379–93
    [Google Scholar]
  59. 59.
    Somova LM, Kondrashova NM, Plekhova NG, Drobot EI, Lyapun IN. 2013. Pathomorphosis of experimental infection in mice, infected by Streptococcus pneumoniae, under the effect of immunotropic drugs. Bull. Exp. Biol. Med. 155:477–83
    [Google Scholar]
  60. 60.
    Mrochen DM, Fernandes de Oliveira LM, Raafat D, Holtfreter S. 2020. Staphylococcus aureus host tropism and its implications for murine infection models. Int. J. Mol. Sci. 21:7061
    [Google Scholar]
  61. 61.
    Kim HK, Missiakas D, Schneewind O. 2014. Mouse models for infectious diseases caused by Staphylococcus aureus. J. Immunol. Methods 410:88–99
    [Google Scholar]
  62. 62.
    Radovanovic I, Mullick A, Gros P. 2011. Genetic control of susceptibility to infection with Candida albicans in mice. PLOS ONE 6:e18957
    [Google Scholar]
  63. 63.
    Gaffen SL, Moutsopoulos NM. 2020. Regulation of host-microbe interactions at oral mucosal barriers by type 17 immunity. Sci. Immunol. 5:eaau4594
    [Google Scholar]
  64. 64.
    Hayes CK, Wilcox DR, Yang Y, Coleman GK, Brown MA, Longnecker R. 2021. ASC-dependent inflammasomes contribute to immunopathology and mortality in herpes simplex encephalitis. PLOS Pathog. 17:e1009285
    [Google Scholar]
  65. 65.
    Montes de Oca M, de Labastida Rivera F, Winterford C, Frame TCM, Ng SS et al. 2020. IL-27 signalling regulates glycolysis in Th1 cells to limit immunopathology during infection. PLOS Pathog. 16:e1008994
    [Google Scholar]
  66. 66.
    Chen M, Sun H, Boot M, Shao L, Chang SJ et al. 2020. Itaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella. Science 369:450–55
    [Google Scholar]
  67. 67.
    Krammer F, Smith GJD, Fouchier RAM, Peiris M, Kedzierska K et al. 2018. Influenza. Nat. Rev. Dis. Primers 4:13
    [Google Scholar]
  68. 68.
    Graham AL. 2021. Naturalizing mouse models for immunology. Nat. Immunol. 22:111–17
    [Google Scholar]
  69. 69.
    Fischer AW, Cannon B, Nedergaard J. 2018. Optimal housing temperatures for mice to mimic the thermal environment of humans: an experimental study. Mol. Metab. 7:161–70
    [Google Scholar]
  70. 70.
    Hopwood TW, Hall S, Begley N, Forman R, Brown S et al. 2018. The circadian regulator BMAL1 programmes responses to parasitic worm infection via a dendritic cell clock. Sci. Rep. 8:3782
    [Google Scholar]
  71. 71.
    Druzd D, Matveeva O, Ince L, Harrison U, He W et al. 2017. Lymphocyte circadian clocks control lymph node trafficking and adaptive immune responses. Immunity 46:120–32
    [Google Scholar]
  72. 72.
    Knudsen NH, Stanya KJ, Hyde AL, Chalom MM, Alexander RK et al. 2020. Interleukin-13 drives metabolic conditioning of muscle to endurance exercise. Science 368:eaat3987
    [Google Scholar]
  73. 73.
    Witjes VM, Boleij A, Halffman W. 2020. Reducing versus embracing variation as strategies for reproducibility: the microbiome of laboratory mice. Animals 10:122415
    [Google Scholar]
  74. 74.
    Jeyakumar T, Beauchemin N, Gros P. 2019. Impact of the microbiome on the human genome. Trends Parasitol. 35:809–21
    [Google Scholar]
  75. 75.
    MacDuff DA, Reese TA, Kimmey JM, Weiss LA, Song C et al. 2015. Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection. eLife 4:e04494
    [Google Scholar]
  76. 76.
    Fallon MT, Benjamin WH, Schoeb TR, Briles DE. 1991. Mouse hepatitis virus strain UAB infection enhances resistance to Salmonella typhimurium in mice by inducing suppression of bacterial growth. Infect. Immun. 59:852–56
    [Google Scholar]
  77. 77.
    Barton ES, White DW, Cathelyn JS, Brett-McClellan KA, Engle M et al. 2007. Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 447:326–29
    [Google Scholar]
  78. 78.
    Hamilton SE, Badovinac VP, Beura LK, Pierson M, Jameson SC et al. 2020. New insights into the immune system using dirty mice. J. Immunol. 205:3–11
    [Google Scholar]
  79. 79.
    Lin J-D, Devlin JC, Yeung F, McCauley C, Leung JM et al. 2020. Rewilding Nod2 and Atg16l1 mutant mice uncovers genetic and environmental contributions to microbial responses and immune cell composition. Cell Host Microbe 27:830–40
    [Google Scholar]
  80. 80.
    Casanova JL, Zhang Q, Bastard P, Jouanguy E 2022. In memoriam: Stephen J Seligman, MD. J. Clin. Immunol. 42:437–40
    [Google Scholar]
  81. 81.
    Gothe F, Howarth S, Duncan CJ, Hambleton S. 2021. Monogenic susceptibility to live viral vaccines. Curr. Opin. Immunol. 72:167–75
    [Google Scholar]
  82. 82.
    Bastard P, Michailidis E, Hoffmann HH, Chbihi M, Le Voyer T et al. 2021. Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine. J. Exp. Med. 218:e20202486
    [Google Scholar]
  83. 83.
    Zhang YE, Vibranovski MD, Landback P, Marais GA, Long M. 2010. Chromosomal redistribution of male-biased genes in mammalian evolution with two bursts of gene gain on the X chromosome. PLOS Biol. 8:e1000494
    [Google Scholar]
  84. 84.
    Nei M, Xu P, Glazko G. 2001. Estimation of divergence times from multiprotein sequences for a few mammalian species and several distantly related organisms. PNAS 98:2497–502
    [Google Scholar]
  85. 85.
    White TD, Asfaw B, Beyene Y, Haile-Selassie Y, Lovejoy CO et al. 2009. Ardipithecus ramidus and the paleobiology of early hominids. Science 326:64–86
    [Google Scholar]
  86. 86.
    Love GD, Grosjean E, Stalvies C, Fike DA, Grotzinger JP et al. 2009. Fossil steroids record the appearance of Demospongiae during the Cryogenian period. Nature 457:718–21
    [Google Scholar]
  87. 87.
    Smith JJ, Kuraku S, Holt C, Sauka-Spengler T, Jiang N et al. 2013. Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution. Nat. Genet. 45:415–21
    [Google Scholar]
  88. 88.
    Anderson PS, Friedman M, Brazeau MD, Rayfield EJ. 2011. Initial radiation of jaws demonstrated stability despite faunal and environmental change. Nature 476:206–9
    [Google Scholar]
  89. 89.
    Churakov G, Sadasivuni MK, Rosenbloom KR, Huchon D, Brosius J, Schmitz J. 2010. Rodent evolution: back to the root. Mol. Biol. Evol. 27:1315–26
    [Google Scholar]
  90. 90.
    Boursot P, Auffray JC, Britton-Davidian J, Bonhomme F. 1993. The evolution of house mice. Ann. Rev. Ecol. Syst. 24:119–52
    [Google Scholar]
  91. 91.
    Kolishovski G, Lamoureux A, Hale P, Richardson JE, Recla JM et al. 2019. The JAX Synteny Browser for mouse-human comparative genomics. Mamm. Genome 30:353–61
    [Google Scholar]
  92. 92.
    Emes RD, Goodstadt L, Winter EE, Ponting CP. 2003. Comparison of the genomes of human and mouse lays the foundation of genome zoology. Hum. Mol. Genet. 12:701–9
    [Google Scholar]
  93. 93.
    Zhang X, Firestein S. 2002. The olfactory receptor gene superfamily of the mouse. Nat. Neurosci. 5:124–33
    [Google Scholar]
  94. 94.
    Young JM, Friedman C, Williams EM, Ross JA, Tonnes-Priddy L, Trask BJ. 2002. Different evolutionary processes shaped the mouse and human olfactory receptor gene families. Hum. Mol. Genet. 11:535–46
    [Google Scholar]
  95. 95.
    Westgaard IH, Berg SF, Ørstavik S, Fossum S, Dissen E. 1998. Identification of a human member of the Ly-49 multigene family. Eur. J. Immunol. 28:1839–46
    [Google Scholar]
  96. 96.
    Higuchi DA, Cahan P, Gao J, Ferris ST, Poursine-Laurent J et al. 2010. Structural variation of the mouse natural killer gene complex. . Genes Immun. 11:8637–48
    [Google Scholar]
  97. 97.
    Yawata M, Yawata N, Abi-Rached L, Parham P. 2002. Variation within the human killer cell immunoglobulin-like receptor (KIR) gene family. Crit. Rev. Immunol. 22:5–6463–82
    [Google Scholar]
  98. 98.
    Webb JR, Lee SH, Vidal SM. 2002. Genetic control of innate immune responses against cytomegalovirus: MCMV meets its match. Genes Immun 3:5250–62
    [Google Scholar]
  99. 99.
    Growney JD, Dietrich WF. 2000. High-resolution genetic and physical map of the Lgn1 interval in C57BL/6J implicates Naip2 or Naip5 in Legionella pneumophila pathogenesis. Genome Res. 10:1158–71
    [Google Scholar]
  100. 100.
    Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF et al. 2002. Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–62
    [Google Scholar]
  101. 101.
    Yeager M, Hughes AL. 1999. Evolution of the mammalian MHC: natural selection, recombination, and convergent evolution. Immunol. Rev. 167:45–58
    [Google Scholar]
  102. 102.
    Mashimo T, Simon-Chazottes D, Guénet JL. 2008. Innate resistance to flavivirus infections and the functions of 2′-5′ oligoadenylate synthetases. Curr. Top. Microbiol. Immunol. 321:85–100
    [Google Scholar]
  103. 103.
    Cotton RN, Shahine A, Rossjohn J, Moody DB. 2018. Lipids hide or step aside for CD1-autoreactive T cell receptors. Curr. Opin. Immunol. 52:93–99
    [Google Scholar]
  104. 104.
    Hardy MP, Owczarek CM, Jermiin LS, Ejdebäck M, Hertzog PJ. 2004. Characterization of the type I interferon locus and identification of novel genes. Genomics 84:331–45
    [Google Scholar]
  105. 105.
    Oritani K, Kincade PW, Zhang C, Tomiyama Y, Matsuzawa Y. 2001. Type I interferons and limitin: a comparison of structures, receptors, and functions. Cytokine Growth Factor Rev. 12:337–48
    [Google Scholar]
  106. 106.
    Oritani K, Medina KL, Tomiyama Y, Ishikawa J, Okajima Y et al. 2000. Limitin: an interferon-like cytokine that preferentially influences B-lymphocyte precursors. Nat. Med. 6:659–66
    [Google Scholar]
  107. 107.
    Xu L, Yang L, Liu W 2013. Distinct evolution process among type I interferon in mammals. Protein Cell 4:5383–92
    [Google Scholar]
  108. 108.
    Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B et al. 2008. Lymphoproliferative disease and autoimmunity in mice with increased miR-17–92 expression in lymphocytes. Nat. Immunol. 9:405–14
    [Google Scholar]
  109. 109.
    Ventura A, Young AG, Winslow MM, Lintault L, Meissner A et al. 2008. Targeted deletion reveals essential and overlapping functions of the miR-17 ∼92 family of miRNA clusters. Cell 132:875–86
    [Google Scholar]
  110. 110.
    Chandan K, Gupta M, Sarwat M. 2020. Role of host and pathogen-derived microRNAs in immune regulation during infectious and inflammatory diseases. Front. Immunol. 10:3081
    [Google Scholar]
  111. 111.
    Le Pendu J, Ruvoën-Clouet N 2020. Fondness for sugars of enteric viruses confronts them with human glycans genetic diversity. Hum. Genet. 139:903–10
    [Google Scholar]
  112. 112.
    Kaur H, Sehgal R, Rani S 2019. Duffy antigen receptor for chemokines (DARC) and susceptibility to Plasmodium vivax malaria. Parasitol. Int. 71:73–75
    [Google Scholar]
  113. 113.
    Torre S, Langlais D, Gros P. 2018. Genetic analysis of cerebral malaria in the mouse model infected with Plasmodium berghei. Mamm. Genome 29:488–506
    [Google Scholar]
  114. 114.
    Min-Oo G, Gros P 2005. Erythrocyte variants and the nature of their malaria protective effect. Cell. Microbiol. 7:753–63
    [Google Scholar]
  115. 115.
    López C, Saravia C, Gomez A, Hoebeke J, Patarroyo MA. 2010. Mechanisms of genetically-based resistance to malaria. Gene 467:1–12
    [Google Scholar]
  116. 116.
    Phifer-Rixey M, Nachman MW. 2015. Insights into mammalian biology from the wild house mouse Mus musculus. eLife 4:e05959
    [Google Scholar]
  117. 117.
    Frazer KA, Eskin E, Kang HM, Bogue MA, Hinds DA et al. 2007. A sequence-based variation map of 8.27 million SNPs in inbred mouse strains. Nature 448:1050–53
    [Google Scholar]
  118. 118.
    Beck JA, Lloyd S, Hafezparast M, Lennon-Pierce M, Eppig JT et al. 2000. Genealogies of mouse inbred strains. Nat. Genet. 24:23–25
    [Google Scholar]
  119. 119.
    Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S et al. 2011. Non-canonical inflammasome activation targets caspase-11. Nature 479:117–21
    [Google Scholar]
  120. 120.
    Broz P, Ruby T, Belhocine K, Bouley DM, Kayagaki N et al. 2012. Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1. Nature 490:288–91
    [Google Scholar]
  121. 121.
    Malo D, Vogan K, Vidal S, Hu J, Cellier M et al. 1994. Haplotype mapping and sequence analysis of the mouse Nramp gene predict susceptibility to infection with intracellular parasites. Genomics 23:51–61
    [Google Scholar]
  122. 122.
    Patel SN, Berghout J, Lovegrove FE, Ayi K, Conroy A et al. 2008. C5 deficiency and C5a or C5aR blockade protects against cerebral malaria. J. Exp. Med. 205:1133–43
    [Google Scholar]
  123. 123.
    Radovanovic I, Leung V, Iliescu A, Bongfen SE, Mullick A et al. 2014. Genetic control of susceptibility to Candida albicans in SM/J mice. J. Immunol. 193:1290–300
    [Google Scholar]
  124. 124.
    Fortin A, Diez E, Rochefort D, Laroche L, Malo D et al. 2001. Recombinant congenic strains derived from A/J and C57BL/6J: a tool for genetic dissection of complex traits. Genomics 74:21–35
    [Google Scholar]
  125. 125.
    Fortin A, Belouchi A, Tam MF, Cardon L, Skamene E et al. 1997. Genetic control of blood parasitaemia in mouse malaria maps to chromosome 8. Nat. Genet. 17:382–83
    [Google Scholar]
  126. 126.
    Foote SJ, Burt RA, Baldwin TM, Presente A, Roberts AW et al. 1997. Mouse loci for malaria-induced mortality and the control of parasitaemia. Nat. Genet. 17:380–81
    [Google Scholar]
  127. 127.
    Ciancanelli MJ, Abel L, Zhang SY, Casanova JL. 2016. Host genetics of severe influenza: from mouse Mx1 to human IRF7. Curr. Opin. Immunol. 38:109–20
    [Google Scholar]
  128. 128.
    Torre S, van Bruggen R, Kennedy JM, Berghout J, Bongfen SE et al. 2013. Susceptibility to lethal cerebral malaria is regulated by epistatic interaction between chromosome 4 (Berr6) and chromosome 1 (Berr7) loci in mice. Genes Immun 14:249–57
    [Google Scholar]
  129. 129.
    Poltorak A, He X, Smirnova I, Liu M-Y, Van Huffel C et al. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–88
    [Google Scholar]
  130. 130.
    Thomas JD, Smith CIE, Sideras P, Vořechovský I, Chapman V, Paul WE. 1993. Colocalization of X-linked agammaglobulinemia and X-linked immunodeficiency genes. Science 261:355–58
    [Google Scholar]
  131. 131.
    Rawlings DJ, Saffran DC, Tsukada S, Largaespada DA. 1993. Mutation of unique region of Bruton's tyrosine kinase in immunodeficient XID mice. Science 261:358–61
    [Google Scholar]
  132. 132.
    Brunkow ME, Jeffery EW, Hjerrild KA, Paeper B, Clark LB et al. 2001. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 27:68–73
    [Google Scholar]
  133. 133.
    Wildin RS, Ramsdell F, Peake J, Faravelli F, Casanova JL et al. 2001. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat. Genet. 27:18–20
    [Google Scholar]
  134. 134.
    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]
  135. 135.
    Mahajan VS, Demissie E, Mattoo H, Viswanadham V, Varki A et al. 2016. Striking immune phenotypes in gene-targeted mice are driven by a copy-number variant originating from a commercially available C57BL/6 strain. Cell Rep. 15:1901–9
    [Google Scholar]
  136. 136.
    Turcotte K, Gauthier S, Mitsos LM, Shustik C, Copeland NG et al. 2004. Genetic control of myeloproliferation in BXH-2 mice. Blood 103:2343–50
    [Google Scholar]
  137. 137.
    Turcotte K, Gauthier S, Tuite A, Mullick A, Malo D, Gros P. 2005. A mutation in the Icsbp1 gene causes susceptibility to infection and a chronic myeloid leukemia-like syndrome in BXH-2 mice. J. Exp. Med. 201:881–90
    [Google Scholar]
  138. 138.
    Tailor P, Tamura T, Morse HC 3rd, Ozato K. 2008. The BXH2 mutation in IRF8 differentially impairs dendritic cell subset development in the mouse. Blood 111:1942–45
    [Google Scholar]
  139. 139.
    Salem S, Salem D, Gros P. 2020. Role of IRF8 in immune cells functions, protection against infections, and susceptibility to inflammatory diseases. Hum. Genet. 139:707–21
    [Google Scholar]
  140. 140.
    Hambleton S, Salem S, Bustamante J, Bigley V, Boisson-Dupuis S et al. 2011. IRF8 mutations and human dendritic-cell immunodeficiency. N. Engl. J. Med. 365:127–38
    [Google Scholar]
  141. 141.
    Brown MG, Dokun AO, Heusel JW, Smith HR, Beckman DL et al. 2001. Vital involvement of a natural killer cell activation receptor in resistance to viral infection. Science 292:5518934–37
    [Google Scholar]
  142. 142.
    Min-Oo G, Fortin A, Tam MF, Nantel A, Stevenson MM, Gros P. 2003. Pyruvate kinase deficiency in mice protects against malaria. Nat. Genet. 35:357–62
    [Google Scholar]
  143. 143.
    Fortin A, Cardon LR, Tam M, Skamene E, Stevenson MM, Gros P. 2001. Identification of a new malaria susceptibility locus (Char4) in recombinant congenic strains of mice. PNAS 98:10793–8
    [Google Scholar]
  144. 144.
    Min-Oo G, Fortin A, Pitari G, Tam M, Stevenson MM, Gros P. 2007. Complex genetic control of susceptibility to malaria: positional cloning of the Char9 locus. J. Exp. Med. 204:511–24
    [Google Scholar]
  145. 145.
    Laroque A, Min-Oo G, Tam M, Ponka P, Stevenson MM, Gros P. 2017. The mouse Char10 locus regulates severity of pyruvate kinase deficiency and susceptibility to malaria. PLOS ONE 12:e0177818
    [Google Scholar]
  146. 146.
    Huang HM, McMorran BJ, Foote SJ, Burgio G. 2018. Host genetics in malaria: lessons from mouse studies. Mamm. Genome 29:507–22
    [Google Scholar]
  147. 147.
    Torre S, Faucher SP, Fodil N, Bongfen SE, Berghout J et al. 2015. THEMIS is required for pathogenesis of cerebral malaria and protection against pulmonary tuberculosis. Infect. Immun. 83:759–68
    [Google Scholar]
  148. 148.
    Kennedy JM, Georges A, Bassenden AV, Vidal SM, Berghuis AM et al. 2020. ZBTB7B (ThPOK) is required for pathogenesis of cerebral malaria and protection against pulmonary tuberculosis. Infect. Immun. 88:e00845–19
    [Google Scholar]
  149. 149.
    Bongfen SE, Rodrigue-Gervais IG, Berghout J, Torre S, Cingolani P et al. 2012. An N-ethyl-N-nitrosourea (ENU)-induced dominant negative mutation in the JAK3 kinase protects against cerebral malaria. PLOS ONE 7:e31012
    [Google Scholar]
  150. 150.
    Olivier JF, Fodil N, Al Habyan S, Gopal A, Artusa P et al. 2020. CCDC88B is required for mobility and inflammatory functions of dendritic cells. J. Leukoc. Biol. 108:1787–802
    [Google Scholar]
  151. 151.
    Kennedy JM, Fodil N, Torre S, Bongfen SE, Olivier JF et al. 2014. CCDC88B is a novel regulator of maturation and effector functions of T cells during pathological inflammation. J. Exp. Med. 211:2519–35
    [Google Scholar]
  152. 152.
    Torre S, Polyak MJ, Langlais D, Fodil N, Kennedy JM et al. 2017. USP15 regulates type I interferon response and is required for pathogenesis of neuroinflammation. Nat. Immunol. 18:54–63
    [Google Scholar]
  153. 153.
    Hoebe K, Beutler B. 2008. Forward genetic analysis of TLR-signaling pathways: an evaluation. Adv. Drug. Deliv. Rev. 60:824–29
    [Google Scholar]
  154. 154.
    Crozat K, Georgel P, Rutschmann S, Mann N, Du X et al. 2006. Analysis of the MCMV resistome by ENU mutagenesis. Mamm. Genome 17:398–406
    [Google Scholar]
  155. 155.
    Wang T, Bu CH, Hildebrand S, Jia G, Siggs OM et al. 2018. Probability of phenotypically detectable protein damage by ENU-induced mutations in the Mutagenetix database. Nat. Commun. 9:441
    [Google Scholar]
  156. 156.
    Arnold CN, Barnes MJ, Berger M, Blasius AL, Brandl K et al. 2012. ENU-induced phenovariance in mice: inferences from 587 mutations. BMC Res. Notes 5:577
    [Google Scholar]
  157. 157.
    Papathanasiou P, Goodnow CC. 2005. Connecting mammalian genome with phenome by ENU mouse mutagenesis: gene combinations specifying the immune system. Annu. Rev. Genet. 39:241–62
    [Google Scholar]
  158. 158.
    Mitsos LM, Cardon LR, Ryan L, LaCourse R, North RJ, Gros P. 2003. Susceptibility to tuberculosis: a locus on mouse chromosome 19 (Trl-4) regulates Mycobacterium tuberculosis replication in the lungs. PNAS 100:6610–15
    [Google Scholar]
  159. 159.
    Marquis J-F, LaCourse R, Ryan L, North RJ, Gros P. 2009. Genetic and functional characterization of the mouse Trl3 locus in defense against tuberculosis. J. Immunol. 182:3757–67
    [Google Scholar]
  160. 160.
    Potter M, O'Brien AD, Skamene E, Gros P, Forget A et al. 1983. A BALB/c congenic strain of mice that carries a genetic locus (Ityr) controlling resistance to intracellular parasites. Infect. Immun. 40:1234–35
    [Google Scholar]
  161. 161.
    Xu G, van Bruggen R, Gualtieri CO, Moradin N, Fois A et al. 2020. Bisphosphoglycerate mutase deficiency protects against cerebral malaria and severe malaria-induced anemia. Cell Rep. 32:108170
    [Google Scholar]
  162. 162.
    Kibar Z, Vogan KJ, Groulx N, Justice MJ, Underhill DA, Gros P. 2001. Ltap, a mammalian homolog of Drosophila Strabismus/Van Gogh, is altered in the mouse neural tube mutant Loop-tail. Nat. Genet. 28:251–55
    [Google Scholar]
  163. 163.
    Epstein DJ, Vekemans M, Gros P. 1991. splotch (Sp2H), a mutation affecting development of the mouse neural tube, shows a deletion within the paired homeodomain of Pax-3. Cell 67:767–74
    [Google Scholar]
  164. 164.
    Lewis G, Rapsomaniki E, Bouriez T, Crockford T, Ferry H et al. 2004. Hyper IgE in New Zealand black mice due to a dominant-negative CD23 mutation. Immunogenetics 56:564–71
    [Google Scholar]
  165. 165.
    Meng G, Zhang F, Fuss I, Kitani A, Strober W. 2009. A mutation in the Nlrp3 gene causing inflammasome hyperactivation potentiates Th17 cell-dominant immune responses. Immunity 30:860–74
    [Google Scholar]
  166. 166.
    Stripecke R, Münz C, Schuringa JJ, Bissig K-D, Soper B et al. 2020. Innovations, challenges, and minimal information for standardization of humanized mice. EMBO Mol. Med. 12:e8662
    [Google Scholar]
  167. 167.
    Li Y, Di Santo JP. 2019. Modeling infectious diseases in mice with a “humanized” immune system. Microbiol. Spectr. 7: https://doi.org/10.1128/microbiolspec.BAI-0019-2019
    [Google Scholar]
  168. 168.
    Allen TM, Brehm MA, Bridges S, Ferguson S, Kumar P et al. 2019. Humanized immune system mouse models: progress, challenges and opportunities. Nat. Immunol. 20:770–74
    [Google Scholar]
  169. 169.
    Chen Q, Amaladoss A, Ye W, Liu M, Dummler S et al. 2014. Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells. PNAS 111:1479–84
    [Google Scholar]
  170. 170.
    Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A et al. 2015. An integrated map of structural variation in 2,504 human genomes. Nature 526:75–81
    [Google Scholar]
  171. 171.
    Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alfoldi J et al. 2021. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581:434–43
    [Google Scholar]
  172. 172.
    Collins RL, Brand H, Karczewski KJ, Zhao X, Alföldi J et al. 2020. A structural variation reference for medical and population genetics. Nature 581:444–51. Erratum 2021. Nature 590:E55
    [Google Scholar]
  173. 173.
    Berberich AJ, Ho R, Hegele RA. 2018. Whole genome sequencing in the clinic: empowerment or too much information?. CMAJ 190:E124–25
    [Google Scholar]
  174. 174.
    Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM et al. 2015. A global reference for human genetic variation. Nature 526:68–74
    [Google Scholar]
  175. 175.
    Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM et al. 2012. An integrated map of genetic variation from 1,092 human genomes. Nature 491:56–65
    [Google Scholar]
  176. 176.
    Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM et al. 2010. A map of human genome variation from population-scale sequencing. Nature 467:1061–73
    [Google Scholar]
  177. 177.
    Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR et al. 2009. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. PNAS 106:19096–101
    [Google Scholar]
  178. 178.
    Shendure J, Waterston RH, Balasubramanian S, Church GM, Gilbert W et al. 2019. DNA sequencing at 40: past, present and future. Nature 550:345–53. Erratum 2019. Nature 568:E11
    [Google Scholar]
  179. 179.
    Belkadi A, Bolze A, Itan Y, Cobat A, Vincent QB et al. 2015. Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants. PNAS 112:5473–78
    [Google Scholar]
  180. 180.
    Casanova J-L, Abel L 2021. Lethal infectious diseases as inborn errors of immunity: toward a synthesis of the germ and genetic theories. Annu. Rev. Pathol. Mech. Dis. 16:23–50
    [Google Scholar]
  181. 181.
    Casanova JL, Abel L. 2022. From rare disorders of immunity to common determinants of infection: following the mechanistic thread. Cell 185:173086–103
    [Google Scholar]
  182. 181a.
    Meyts I 2022. Null IFNAR1 and IFNAR2 alleles are surprisingly common in the Pacific and Arctic. J. Exp. Med 219:6e20220491
    [Google Scholar]
  183. 181b.
    Duncan CJA, Skouboe MK, Howarth S, Hollensen AK, Chen Ret al 2022. Life-threatening viral disease in a novel form of autosomal recessive IFNAR2 deficiency in the Arctic. J. Exp. Med 219:6e20212427
    [Google Scholar]
  184. 181c.
    Bastard P, Hsiao KC, Zhang Q, Choin J, Best Eet al 2022. A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes. J. Exp. Med 219:6e20220028
    [Google Scholar]
  185. 182.
    Knapp KM, Sullivan R, Murray J, Gimenez G, Arn P et al. 2020. Linked-read genome sequencing identifies biallelic pathogenic variants in DONSON as a novel cause of Meier-Gorlin syndrome. J. Med. Genet. 57:3195–202
    [Google Scholar]
  186. 183.
    Yusuff T, Kellaris G, Girirajan S, Katsanis N. 2021. Dissecting the complexity of CNV pathogenicity: insights from Drosophila and zebrafish models. Curr. Opin. Genet. Dev. 68:79–87
    [Google Scholar]
  187. 184.
    MacArthur DG, Balasubramanian S, Frankish A, Huang N, Morris J et al. 2012. A systematic survey of loss-of-function variants in human protein-coding genes. Science 335:823–28
    [Google Scholar]
  188. 185.
    Rapaport F, Boisson B, Gregor A, Béziat V, Boisson-Dupuis S et al. 2021. Negative selection on human genes underlying inborn errors depends on disease outcome and both the mode and mechanism of inheritance. PNAS 118:e2001248118
    [Google Scholar]
  189. 186.
    Casanova J-L, Abel L 2020. The human genetic determinism of life-threatening infectious diseases: genetic heterogeneity and physiological homogeneity?. Hum. Genet. 139:681–94
    [Google Scholar]
  190. 187.
    Casanova JL. 2015. Human genetic basis of interindividual variability in the course of infection. PNAS 112:7118–27
    [Google Scholar]
  191. 188.
    Casanova JL. 2015. Severe infectious diseases of childhood as monogenic inborn errors of immunity. PNAS 112:7128–37
    [Google Scholar]
  192. 189.
    Allison AC. 1954. Protection afforded by sickle-cell trait against subtertian malarial infection. Br. Med. J. 1:290–94
    [Google Scholar]
  193. 190.
    Schwerk J, Negash A, Savan R, Gale M Jr. 2021. Innate immunity in hepatitis C virus infection. Cold Spring Harb. Perspect. Med. 11:a036988
    [Google Scholar]
  194. 191.
    Vidal SM, Malo D, Marquis JF, Gros P. 2008. Forward genetic dissection of immunity to infection in the mouse. Annu. Rev. Immunol. 26:81–132
    [Google Scholar]
  195. 192.
    Puel A, Bastard P, Bustamante J, Casanova JL. 2022. Human autoantibodies underlying infectious diseases. J. Exp. Med. 219:4e20211387
    [Google Scholar]
  196. 193.
    Bastard P, Orlova E, Sozaeva L, Lévy R, James A et al. 2021. Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1. J. Exp. Med. 218:e20210554
    [Google Scholar]
  197. 194.
    Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann H-H et al. 2020. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science 370:eabd4585
    [Google Scholar]
  198. 195.
    Ku CL, Chi CY, von Bernuth H, Doffinger R. 2020. Autoantibodies against cytokines: phenocopies of primary immunodeficiencies?. Hum. Genet. 139:783–94
    [Google Scholar]
  199. 196.
    Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G et al. 2007. TLR3 deficiency in patients with herpes simplex encephalitis. Science 317:1522–27
    [Google Scholar]
  200. 197.
    Casrouge A, Zhang SY, Eidenschenk C, Jouanguy E, Puel A et al. 2006. Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 314:308–12
    [Google Scholar]
  201. 198.
    Zhang S-Y, Casanova J-L. 2015. Inborn errors underlying herpes simplex encephalitis: from TLR3 to IRF3. J. Exp. Med. 212:1342–43
    [Google Scholar]
  202. 199.
    Bastard P, Manry J, Chen J, Rosain J, Seeleuthner Y et al. 2021. Herpes simplex encephalitis in a patient with a distinctive form of inherited IFNAR1 deficiency. J. Clin. Investig. 131:e139980
    [Google Scholar]
  203. 200.
    Lafaille FG, Pessach IM, Zhang SY, Ciancanelli MJ, Herman M et al. 2012. Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells. Nature 491:769–73
    [Google Scholar]
  204. 201.
    Zimmer B, Ewaleifoh O, Harschnitz O, Lee YS, Peneau C et al. 2018. Human iPSC-derived trigeminal neurons lack constitutive TLR3-dependent immunity that protects cortical neurons from HSV-1 infection. PNAS 115:E8775–82
    [Google Scholar]
  205. 202.
    Gao D, Ciancanelli MJ, Zhang P, Harschnitz O, Bondet V et al. 2021. TLR3 controls constitutive IFN-β antiviral immunity in human fibroblasts and cortical neurons. J. Clin. Investig. 131:e134529
    [Google Scholar]
  206. 203.
    Lafaille FG, Harschnitz O, Lee YS, Zhang P, Hasek ML et al. 2019. Human SNORA31 variations impair cortical neuron-intrinsic immunity to HSV-1 and underlie herpes simplex encephalitis. Nat. Med. 25:1873–84
    [Google Scholar]
  207. 204.
    Zhang SY, Clark NE, Freije CA, Pauwels E, Taggart AJ et al. 2018. Inborn errors of RNA lariat metabolism in humans with brainstem viral infection. Cell 172:952–65.e18
    [Google Scholar]
  208. 205.
    Mancini M, Caignard G, Charbonneau B, Dumaine A, Wu N et al. 2019. Rel-dependent immune and central nervous system mechanisms control viral replication and inflammation during mouse herpes simplex encephalitis. J. Immunol. 202:1479–93
    [Google Scholar]
  209. 206.
    Sato R, Kato A, Chimura T, Saitoh SI, Shibata T et al. 2018. Combating herpesvirus encephalitis by potentiating a TLR3-mTORC2 axis. Nat. Immunol. 19:1071–82
    [Google Scholar]
  210. 207.
    Bustamante J. 2020. Mendelian susceptibility to mycobacterial disease: recent discoveries. Hum. Genet. 139:993–1000
    [Google Scholar]
  211. 208.
    Nathan CF, Murray HW, Wiebe ME, Rubin BY. 1983. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J. Exp. Med. 158:670–89
    [Google Scholar]
  212. 209.
    Boisson-Dupuis S, Ramirez-Alejo N, Li Z, Patin E, Rao G et al. 2018. Tuberculosis and impaired IL-23-dependent IFN-γ immunity in humans homozygous for a common TYK2 missense variant. Sci. Immunol. 3:eaau8714
    [Google Scholar]
  213. 210.
    Kerner G, Ramirez-Alejo N, Seeleuthner Y, Yang R, Ogishi M et al. 2019. Homozygosity for TYK2 P1104A underlies tuberculosis in about 1% of patients in a cohort of European ancestry. PNAS 116:10430–34
    [Google Scholar]
  214. 211.
    Kerner G, Laval G, Patin E, Boisson-Dupuis S, Abel L et al. 2021. Human ancient DNA analyses reveal the high burden of tuberculosis in Europeans over the last 2,000 years. Am. J. Hum. Genet. 108:517–24
    [Google Scholar]
  215. 212.
    Dalton DK, Pitts-Meek S, Keshav S, Figari IS, Bradley A, Stewart TA. 1993. Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science 259:1739–42
    [Google Scholar]
  216. 213.
    Vidal SM, Malo D, Vogan K, Skamene E, Gros P. 1993. Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell 73:469–85
    [Google Scholar]
  217. 214.
    Casanova JL, Conley ME, Seligman SJ, Abel L, Notarangelo LD 2014. Guidelines for genetic studies in single patients: lessons from primary immunodeficiencies. J. Exp. Med. 211:2137–49
    [Google Scholar]
  218. 215.
    Israel L, Wang Y, Bulek K, Mina ED, Zhang Z et al. 2017. Human adaptive immunity rescues an inborn error of innate immunity. Cell 168:789–800
    [Google Scholar]
  219. 216.
    Drutman SB, Mansouri D, Mahdaviani SA, Neehus A-L, Hum D et al. 2020. Fatal cytomegalovirus infection in an adult with inherited NOS2 deficiency. N. Engl. J. Med. 382:437–45
    [Google Scholar]
  220. 217.
    Ciancanelli MJ, Huang SX, Luthra P, Garner H et al. 2015. Infectious disease: life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. Science 348:448–53
    [Google Scholar]
  221. 218.
    Hernandez N, Melki I, Jing H, Habib T, Huang SSY et al. 2018. Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency. J. Exp. Med. 215:2567–85
    [Google Scholar]
  222. 219.
    Lim HK, Huang SXL, Chen J, Kerner G, Gilliaux O et al. 2019. Severe influenza pneumonitis in children with inherited TLR3 deficiency. J. Exp. Med. 216:2038–56
    [Google Scholar]
  223. 220.
    Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M et al. 2020. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 370:eabd4570
    [Google Scholar]
  224. 221.
    Hernandez N, Bucciol G, Moens L, Le Pen J, Shahrooei M et al. 2019. Inherited IFNAR1 deficiency in otherwise healthy patients with adverse reaction to measles and yellow fever live vaccines. J. Exp. Med. 216:2057–70
    [Google Scholar]
  225. 222.
    Duncan CJ, Mohamad SM, Young DF, Skelton AJ, Leahy TR et al. 2015. Human IFNAR2 deficiency: lessons for antiviral immunity. Sci. Transl. Med. 7:307ra154
    [Google Scholar]
  226. 223.
    Asano T, Boisson B, Onodi F, Matuozzo D, Moncada-Velez M et al. 2021. X-linked recessive TLR7 deficiency in ∼1% of men under 60 years old with life-threatening COVID-19. Sci. Immunol. 6:eabl4348
    [Google Scholar]
  227. 224.
    Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q et al. 2021. Autoantibodies neutralizing type I IFNs are present in ∼4% of uninfected individuals over 70 years old and account for ∼20% of COVID-19 deaths. Sci. Immunol. 6:eabl4340
    [Google Scholar]
  228. 225.
    van der Wijst MGP, Vazquez SE, Hartoularos GC, Bastard P, Grant T et al. 2021. Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19. Sci. Transl. Med 13612eabh2624
    [Google Scholar]
  229. 226.
    Zhang Q, Bastard P, Bolze A, Jouanguy E, Zhang SY et al. 2020. Life-threatening COVID-19: defective interferons unleash excessive inflammation. Med 1:14–20
    [Google Scholar]
  230. 226a.
    Zhang Q, Pizzorno A, Miorin L, Bastard P, Gervais Aet al 2022. Autoantibodies against type I IFNs in patients with critical influenza pneumonia. J. Exp. Med 219:11e20220514
    [Google Scholar]
  231. 227.
    García-Sastre A. 2011. Induction and evasion of type I interferon responses by influenza viruses. Virus Res. 162:12–18
    [Google Scholar]
  232. 228.
    Chen Y, Graf L, Chen T, Liao Q, Bai T et al. 2021. Rare variant MX1 alleles increase human susceptibility to zoonotic H7N9 influenza virus. Science 373:918–922
    [Google Scholar]
  233. 229.
    Van Horebeek L, Dubois B, Goris A. 2019. Somatic variants: new kids on the block in human immunogenetics. Trends Genet. 35:935–47
    [Google Scholar]
  234. 230.
    Aluri J, Cooper MA. 2021. Genetic mosaicism as a cause of inborn errors of immunity. J. Clin. Immunol. 41:718–28
    [Google Scholar]
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