Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus

English version České info

Type I interferons (IFN-I) are innate cytokines crucial for vertebrate antiviral defenses. IFN-I exert antiviral effector functions and orchestrate antiviral immunity. IFN-I are induced early after infection, upon sensing of viral particles or infected cells by immune receptors. Intracellular Toll-like receptors (TLR) are selectively expressed in specialized immune cell types such as plasmacytoid dendritic cells (pDC), enabling them to copiously produce IFN-I upon detection of engulfed viral nucleic acids. pDC or intracellular TLR have been reported to be crucial for resistance to experimental infections with many viruses in mice but dispensable for resistance to natural infections in humans. Our aim was to investigate this puzzling difference. Mice deficient for TLR activity mounted strong IFN-I responses despite producing very low IFN-I levels and controlled the infection by a moderate dose of murine cytomegalovirus much better than mice deficient for IFN-I responses. Deficient TLR responses could be compensated by direct recognition of infected cells by natural killer cells. Hence, we identified experimental conditions in mice mimicking the lack of requirement of TLR functions for antiviral defense observed in humans. We used these experimental models to advance our basic understanding of antiviral immunity in a way that might help improve treatments for patients.

Vyšlo v časopise: Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004897
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004897

Souhrn

Zdroje

1. Tomasello E, Pollet E, Vu Manh T-P, Uzé G, Dalod M. Harnessing mechanistic knowledge on beneficial versus deleterious IFN-I effects to design innovative immunotherapies targeting cytokine activity to specific cell types. Frontiers in Immunology. 2014;5.

2. Zhang SY, Boisson-Dupuis S, Chapgier A, Yang K, Bustamante J, Puel A, et al. Inborn errors of interferon (IFN)-mediated immunity in humans: insights into the respective roles of IFN-alpha/beta, IFN-gamma, and IFN-lambda in host defense. Immunol Rev. 2008;226:29–40. doi: 10.1111/j.1600-065X.2008.00698.x 19161414

3. Mordstein M, Kochs G, Dumoutier L, Renauld JC, Paludan SR, Klucher K, et al. Interferon-lambda contributes to innate immunity of mice against influenza A virus but not against hepatotropic viruses. PLoS pathogens. 2008;4(9):e1000151. doi: 10.1371/journal.ppat.1000151 18787692

4. Pott J, Mahlakoiv T, Mordstein M, Duerr CU, Michiels T, Stockinger S, et al. IFN-lambda determines the intestinal epithelial antiviral host defense. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(19):7944–9. doi: 10.1073/pnas.1100552108 21518880

5. Alexandre YO, Cocita CD, Ghilas S, Dalod M. Deciphering the role of DC subsets in MCMV infection to better understand immune protection against viral infections. Frontiers in microbiology. 2014;5:378. doi: 10.3389/fmicb.2014.00378 25120535

6. Ku CL, von Bernuth H, Picard C, Zhang SY, Chang HH, Yang K, et al. Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. The Journal of experimental medicine. 2007;204(10):2407–22. 17893200

7. von Bernuth H, Picard C, Jin Z, Pankla R, Xiao H, Ku CL, et al. Pyogenic bacterial infections in humans with MyD88 deficiency. Science. 2008;321(5889):691–6. doi: 10.1126/science.1158298 18669862

8. von Bernuth H, Picard C, Puel A, Casanova JL. Experimental and natural infections in MyD88- and IRAK-4-deficient mice and humans. European journal of immunology. 2012;42(12):3126–35. doi: 10.1002/eji.201242683 23255009

9. Garlanda C, Dinarello CA, Mantovani A. The interleukin-1 family: back to the future. Immunity. 2013;39(6):1003–18. doi: 10.1016/j.immuni.2013.11.010 24332029

10. Dalod M, Salazar-Mather TP, Malmgaard L, Lewis C, Asselin-Paturel C, Briere F, et al. Interferon alpha/beta and interleukin 12 responses to viral infections: pathways regulating dendritic cell cytokine expression in vivo. The Journal of experimental medicine. 2002;195(4):517–28. 11854364

11. Baranek T, Zucchini N, Dalod M. Plasmacytoid dendritic cells and the control of herpesvirus infections. Viruses. 2009;1(3):383–419. doi: 10.3390/v1030383 21994554

12. Swiecki M, Wang Y, Gilfillan S, Colonna M. Plasmacytoid dendritic cells contribute to systemic but not local antiviral responses to HSV infections. PLoS pathogens. 2013;9(10):e1003728. doi: 10.1371/journal.ppat.1003728 24204273

13. Cervantes-Barragan L, Zust R, Weber F, Spiegel M, Lang KS, Akira S, et al. Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon. Blood. 2007;109(3):1131–7. 16985170

14. Cervantes-Barragan L, Lewis KL, Firner S, Thiel V, Hugues S, Reith W, et al. Plasmacytoid dendritic cells control T-cell response to chronic viral infection. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(8):3012–7. doi: 10.1073/pnas.1117359109 22315415

15. Blasius AL, Krebs P, Sullivan BM, Oldstone MB, Popkin DL. Slc15a4, a gene required for pDC sensing of TLR ligands, is required to control persistent viral infection. PLoS pathogens. 2012;8(9):e1002915. doi: 10.1371/journal.ppat.1002915 23028315

16. Macal M, Lewis GM, Kunz S, Flavell R, Harker JA, Zuniga EI. Plasmacytoid dendritic cells are productively infected and activated through TLR-7 early after arenavirus infection. Cell host & microbe. 2012;11(6):617–30.

17. Krmpotic A, Bubic I, Polic B, Lucin P, Jonjic S. Pathogenesis of murine cytomegalovirus infection. Microbes Infect. 2003;5(13):1263–77. 14623023

18. Strobl B, Bubic I, Bruns U, Steinborn R, Lajko R, Kolbe T, et al. Novel functions of tyrosine kinase 2 in the antiviral defense against murine cytomegalovirus. Journal of immunology. 2005;175(6):4000–8. 16148148

19. Kropp KA, Robertson KA, Sing G, Rodriguez-Martin S, Blanc M, Lacaze P, et al. Reversible inhibition of murine cytomegalovirus replication by gamma interferon (IFN-gamma) in primary macrophages involves a primed type I IFN-signaling subnetwork for full establishment of an immediate-early antiviral state. Journal of virology. 2011;85(19):10286–99. doi: 10.1128/JVI.00373-11 21775459

20. Blanc M, Hsieh WY, Robertson KA, Watterson S, Shui G, Lacaze P, et al. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. PLoS Biol. 2011;9(3):e1000598. doi: 10.1371/journal.pbio.1000598 21408089

21. Blanc M, Hsieh WY, Robertson KA, Kropp KA, Forster T, Shui G, et al. The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Immunity. 2013;38(1):106–18. doi: 10.1016/j.immuni.2012.11.004 23273843

22. Presti RM, Pollock JL, Dal Canto AJ, O'Guin AK, Virgin HWt. Interferon gamma regulates acute and latent murine cytomegalovirus infection and chronic disease of the great vessels. The Journal of experimental medicine. 1998;188(3):577–88. 9687534

23. Baranek T, Manh TP, Alexandre Y, Maqbool MA, Cabeza JZ, Tomasello E, et al. Differential responses of immune cells to type I interferon contribute to host resistance to viral infection. Cell host & microbe. 2012;12(4):571–84.

24. Krug A, French AR, Barchet W, Fischer JA, Dzionek A, Pingel JT, et al. TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity. 2004;21(1):107–19. 15345224

25. Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, Crozat K, et al. Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(10):3516–21. 14993594

26. Delale T, Paquin A, Asselin-Paturel C, Dalod M, Brizard G, Bates EE, et al. MyD88-dependent and-independent murine cytomegalovirus sensing for IFN-alpha release and initiation of immune responses in vivo. Journal of immunology. 2005;175(10):6723–32. 16272328

27. Zucchini N, Bessou G, Traub S, Robbins SH, Uematsu S, Akira S, et al. Cutting edge: Overlapping functions of TLR7 and TLR9 for innate defense against a herpesvirus infection. Journal of immunology. 2008;180(9):5799–803. 18424698

28. Zucchini N, Bessou G, Robbins SH, Chasson L, Raper A, Crocker PR, et al. Individual plasmacytoid dendritic cells are major contributors to the production of multiple innate cytokines in an organ-specific manner during viral infection. International immunology. 2008;20(1):45–56. 18000008

29. Swiecki M, Gilfillan S, Vermi W, Wang Y, Colonna M. Plasmacytoid dendritic cell ablation impacts early interferon responses and antiviral NK and CD8(+) T cell accrual. Immunity. 2010;33(6):955–66. doi: 10.1016/j.immuni.2010.11.020 21130004

30. Schneider K, Loewendorf A, De Trez C, Fulton J, Rhode A, Shumway H, et al. Lymphotoxin-mediated crosstalk between B cells and splenic stroma promotes the initial type I interferon response to cytomegalovirus. Cell host & microbe. 2008;3(2):67–76.

31. Brown MG, Dokun AO, Heusel JW, Smith HR, Beckman DL, Blattenberger EA, et al. Vital involvement of a natural killer cell activation receptor in resistance to viral infection. Science. 2001;292(5518):934–7. 11340207

32. Chaix J, Tessmer MS, Hoebe K, Fuseri N, Ryffel B, Dalod M, et al. Cutting edge: Priming of NK cells by IL-18. Journal of immunology. 2008;181(3):1627–31. 18641298

33. French AR, Sjolin H, Kim S, Koka R, Yang L, Young DA, et al. DAP12 signaling directly augments proproliferative cytokine stimulation of NK cells during viral infections. Journal of immunology. 2006;177(8):4981–90. 17015680

34. Andrews DM, Scalzo AA, Yokoyama WM, Smyth MJ, Degli-Esposti MA. Functional interactions between dendritic cells and NK cells during viral infection. Nat Immunol. 2003;4(2):175–81. 12496964

35. Madera S, Sun JC. Cutting edge: stage-specific requirement of IL-18 for antiviral NK cell expansion. Journal of immunology. 2015;194(4):1408–12. doi: 10.4049/jimmunol.1402001 25589075

36. Pien GC, Satoskar AR, Takeda K, Akira S, Biron CA. Cutting edge: selective IL-18 requirements for induction of compartmental IFN-gamma responses during viral infection. Journal of immunology. 2000;165(9):4787–91.

37. Pang IK, Ichinohe T, Iwasaki A. IL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8(+) T cell responses to influenza A virus. Nat Immunol. 2013;14(3):246–53. doi: 10.1038/ni.2514 23314004

38. Beutler B, Eidenschenk C, Crozat K, Imler JL, Takeuchi O, Hoffmann JA, et al. Genetic analysis of resistance to viral infection. Nat Rev Immunol. 2007;7(10):753–66. 17893693

39. Robbins SH, Bessou G, Cornillon A, Zucchini N, Rupp B, Ruzsics Z, et al. Natural killer cells promote early CD8 T cell responses against cytomegalovirus. PLoS pathogens. 2007;3(8):e123. 17722980

40. Andrews DM, Estcourt MJ, Andoniou CE, Wikstrom ME, Khong A, Voigt V, et al. Innate immunity defines the capacity of antiviral T cells to limit persistent infection. The Journal of experimental medicine. 2010;207(6):1333–43. doi: 10.1084/jem.20091193 20513749

41. Stadnisky MD, Xie X, Coats ER, Bullock TN, Brown MG. Self MHC class I-licensed NK cells enhance adaptive CD8 T-cell viral immunity. Blood. 2011;117(19):5133–41. doi: 10.1182/blood-2010-12-324632 21436069

42. Mitrovic M, Arapovic J, Traven L, Krmpotic A, Jonjic S. Innate immunity regulates adaptive immune response: lessons learned from studying the interplay between NK and CD8+ T cells during MCMV infection. Medical microbiology and immunology. 2012;201(4):487–95. doi: 10.1007/s00430-012-0263-0 22965169

43. Scalzo AA, Brown MG, Chu DT, Heusel JW, Yokoyama WM, Forbes CA. Development of intra-natural killer complex (NKC) recombinant and congenic mouse strains for mapping and functional analysis of NK cell regulatory loci. Immunogenetics. 1999;49(3):238–41. 9914339

44. Bubic I, Wagner M, Krmpotic A, Saulig T, Kim S, Yokoyama WM, et al. Gain of virulence caused by loss of a gene in murine cytomegalovirus. Journal of virology. 2004;78(14):7536–44. 15220428

45. Handke W, Luig C, Popovic B, Krmpotic A, Jonjic S, Brune W. Viral inhibition of BAK promotes murine cytomegalovirus dissemination to salivary glands. Journal of virology. 2013;87(6):3592–6. doi: 10.1128/JVI.02657-12 23302869

46. Kumagai Y, Takeuchi O, Kato H, Kumar H, Matsui K, Morii E, et al. Alveolar macrophages are the primary interferon-alpha producer in pulmonary infection with RNA viruses. Immunity. 2007;27(2):240–52. 17723216

47. Nguyen KB, Salazar-Mather TP, Dalod MY, Van Deusen JB, Wei XQ, Liew FY, et al. Coordinated and distinct roles for IFN-alpha beta, IL-12, and IL-15 regulation of NK cell responses to viral infection. Journal of immunology. 2002;169(8):4279–87. 12370359

48. Sun JC, Madera S, Bezman NA, Beilke JN, Kaplan MH, Lanier LL. Proinflammatory cytokine signaling required for the generation of natural killer cell memory. The Journal of experimental medicine. 2012;209(5):947–54. doi: 10.1084/jem.20111760 22493516

49. Livingston-Rosanoff D, Daley-Bauer LP, Garcia A, McCormick AL, Huang J, Mocarski ES. Antiviral T cell response triggers cytomegalovirus hepatitis in mice. Journal of virology. 2012;86(23):12879–90. doi: 10.1128/JVI.01752-12 22993151

50. Li Q, Skinner PJ, Ha SJ, Duan L, Mattila TL, Hage A, et al. Visualizing antigen-specific and infected cells in situ predicts outcomes in early viral infection. Science. 2009;323(5922):1726–9. doi: 10.1126/science.1168676 19325114

51. Jordan S, Ruzsics Z, Mitrovic M, Baranek T, Arapovic J, Krmpotic A, et al. Natural killer cells are required for extramedullary hematopoiesis following murine cytomegalovirus infection. Cell host & microbe. 2013;13(5):535–45.

52. Muller U, Steinhoff U, Reis LF, Hemmi S, Pavlovic J, Zinkernagel RM, et al. Functional role of type I and type II interferons in antiviral defense. Science. 1994;264(5167):1918–21. 8009221

53. Dupuis S, Jouanguy E, Al-Hajjar S, Fieschi C, Al-Mohsen IZ, Al-Jumaah S, et al. Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Nature genetics. 2003;33(3):388–91. 12590259

54. Hambleton S, Goodbourn S, Young DF, Dickinson P, Mohamad SM, Valappil M, et al. STAT2 deficiency and susceptibility to viral illness in humans. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(8):3053–8. doi: 10.1073/pnas.1220098110 23391734

55. French AR, Pingel JT, Wagner M, Bubic I, Yang L, Kim S, et al. Escape of mutant double-stranded DNA virus from innate immune control. Immunity. 2004;20(6):747–56. 15189739

56. French AR, Pingel JT, Kim S, Yang L, Yokoyama WM. Rapid emergence of escape mutants following infection with murine cytomegalovirus in immunodeficient mice. Clin Immunol. 2005;115(1):61–9. 15870022

57. Reddehase MJ, Mutter W, Munch K, Buhring HJ, Koszinowski UH. CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity. Journal of virology. 1987;61(10):3102–8. 3041033

58. Pahl-Seibert MF, Juelch M, Podlech J, Thomas D, Deegen P, Reddehase MJ, et al. Highly protective in vivo function of cytomegalovirus IE1 epitope-specific memory CD8 T cells purified by T-cell receptor-based cell sorting. Journal of virology. 2005;79(9):5400–13. 15827154

59. Tay CH, Welsh RM. Distinct organ-dependent mechanisms for the control of murine cytomegalovirus infection by natural killer cells. Journal of virology. 1997;71(1):267–75. 8985346

60. Loh J, Chu DT, O'Guin AK, Yokoyama WM, Virgin HWt. Natural killer cells utilize both perforin and gamma interferon to regulate murine cytomegalovirus infection in the spleen and liver. Journal of virology. 2005;79(1):661–7. 15596864

61. van Dommelen SL, Sumaria N, Schreiber RD, Scalzo AA, Smyth MJ, Degli-Esposti MA. Perforin and granzymes have distinct roles in defensive immunity and immunopathology. Immunity. 2006;25(5):835–48. 17088087

62. Sumaria N, van Dommelen SL, Andoniou CE, Smyth MJ, Scalzo AA, Degli-Esposti MA. The roles of interferon-gamma and perforin in antiviral immunity in mice that differ in genetically determined NK-cell-mediated antiviral activity. Immunol Cell Biol. 2009;87(7):559–66. doi: 10.1038/icb.2009.41 19564888

63. Polic B, Hengel H, Krmpotic A, Trgovcich J, Pavic I, Luccaronin P, et al. Hierarchical and redundant lymphocyte subset control precludes cytomegalovirus replication during latent infection. The Journal of experimental medicine. 1998;188(6):1047–54. 9743523

64. van Dommelen SL, Tabarias HA, Smyth MJ, Degli-Esposti MA. Activation of natural killer (NK) T cells during murine cytomegalovirus infection enhances the antiviral response mediated by NK cells. Journal of virology. 2003;77(3):1877–84. 12525622

65. Wesley JD, Tessmer MS, Chaukos D, Brossay L. NK cell-like behavior of Valpha14i NK T cells during MCMV infection. PLoS pathogens. 2008;4(7):e1000106. doi: 10.1371/journal.ppat.1000106 18636102

66. Tyznik AJ, Tupin E, Nagarajan NA, Her MJ, Benedict CA, Kronenberg M. Cutting edge: the mechanism of invariant NKT cell responses to viral danger signals. Journal of immunology. 2008;181(7):4452–6. 18802047

67. Reilly EC, Thompson EA, Aspeslagh S, Wands JR, Elewaut D, Brossay L. Activated iNKT cells promote memory CD8+ T cell differentiation during viral infection. PloS one. 2012;7(5):e37991. doi: 10.1371/journal.pone.0037991 22649570

68. Tyznik AJ, Verma S, Wang Q, Kronenberg M, Benedict CA. Distinct requirements for activation of NKT and NK cells during viral infection. Journal of immunology. 2014;192(8):3676–85. doi: 10.4049/jimmunol.1300837 24634489

69. Khairallah C, Netzer S, Villacreces A, Juzan M, Rousseau B, Dulanto S, et al. gammadelta T Cells Confer Protection against Murine Cytomegalovirus (MCMV). PLoS pathogens. 2015;11(3):e1004702. doi: 10.1371/journal.ppat.1004702 25747674

70. Sell S, Dietz M, Schneider A, Holtappels R, Mach M, Winkler TH. Control of murine cytomegalovirus infection by gammadelta T cells. PLoS pathogens. 2015;11(2):e1004481. doi: 10.1371/journal.ppat.1004481 25658831

71. Lafarge X, Merville P, Cazin MC, Berge F, Potaux L, Moreau JF, et al. Cytomegalovirus infection in transplant recipients resolves when circulating gammadelta T lymphocytes expand, suggesting a protective antiviral role. The Journal of infectious diseases. 2001;184(5):533–41. 11494158

72. Pitard V, Roumanes D, Lafarge X, Couzi L, Garrigue I, Lafon ME, et al. Long-term expansion of effector/memory Vdelta2-gammadelta T cells is a specific blood signature of CMV infection. Blood. 2008;112(4):1317–24. doi: 10.1182/blood-2008-01-136713 18539896

73. Jost S, Altfeld M. Control of human viral infections by natural killer cells. Annual review of immunology. 2013;31:163–94. doi: 10.1146/annurev-immunol-032712-100001 23298212

74. Puttur F, Arnold-Schrauf C, Lahl K, Solmaz G, Lindenberg M, Mayer CT, et al. Absence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance. PLoS pathogens. 2013;9(9):e1003648. doi: 10.1371/journal.ppat.1003648 24086137

75. Wikstrom ME, Fleming P, Comerford I, McColl SR, Andoniou CE, Degli-Esposti MA. A chemokine-like viral protein enhances alpha interferon production by plasmacytoid dendritic cells but delays CD8+ T cell activation and impairs viral clearance. Journal of virology. 2013;87(14):7911–20. doi: 10.1128/JVI.00187-13 23658453

76. Sun L, Miyoshi H, Origanti S, Nice TJ, Barger AC, Manieri NA, et al. Type I interferons link viral infection to enhanced epithelial turnover and repair. Cell host & microbe. 2015;17(1):85–97.

77. Schenkel JM, Fraser KA, Beura LK, Pauken KE, Vezys V, Masopust D. T cell memory. Resident memory CD8 T cells trigger protective innate and adaptive immune responses. Science. 2014;346(6205):98–101. doi: 10.1126/science.1254536 25170049

78. Ariotti S, Hogenbirk MA, Dijkgraaf FE, Visser LL, Hoekstra ME, Song JY, et al. T cell memory. Skin-resident memory CD8(+) T cells trigger a state of tissue-wide pathogen alert. Science. 2014;346(6205):101–5. doi: 10.1126/science.1254803 25278612

79. Geurs TL, Zhao YM, Hill EB, French AR. Ly49H engagement compensates for the absence of type I interferon signaling in stimulating NK cell proliferation during murine cytomegalovirus infection. Journal of immunology. 2009;183(9):5830–6. doi: 10.4049/jimmunol.0901520 19828630

80. Jordan S, Krause J, Prager A, Mitrovic M, Jonjic S, Koszinowski UH, et al. Virus progeny of murine cytomegalovirus bacterial artificial chromosome pSM3fr show reduced growth in salivary Glands due to a fixed mutation of MCK-2. Journal of virology. 2011;85(19):10346–53. doi: 10.1128/JVI.00545-11 21813614

81. O'Garra A. Systems Approach to Understand the Immune Response in Tuberculosis: An Iterative Process between Mouse Models and Human Disease. Cold Spring Harb Symp Quant Biol. 2013;78:173–7. doi: 10.1101/sqb.2013.78.020172 24100583

82. Zeng M, Haase AT, Schacker TW. Lymphoid tissue structure and HIV-1 infection: life or death for T cells. Trends Immunol. 2012;33(6):306–14. doi: 10.1016/j.it.2012.04.002 22613276

83. Barber DL, Wherry EJ, Ahmed R. Cutting edge: rapid in vivo killing by memory CD8 T cells. Journal of immunology. 2003;171(1):27–31.