A Temporal Role Of Type I Interferon Signaling in CD8 T Cell Maturation during Acute West Nile Virus Infection
A genetic absence of the common IFN- α/β signaling receptor (IFNAR) in mice is associated with enhanced viral replication and altered adaptive immune responses. However, analysis of IFNAR-/- mice is limited for studying the functions of type I IFN at discrete stages of viral infection. To define the temporal functions of type I IFN signaling in the context of infection by West Nile virus (WNV), we treated mice with MAR1-5A3, a neutralizing, non cell-depleting anti-IFNAR antibody. Inhibition of type I IFN signaling at or before day 2 after infection was associated with markedly enhanced viral burden, whereas treatment at day 4 had substantially less effect on WNV dissemination. While antibody treatment prior to infection resulted in massive expansion of virus-specific CD8+ T cells, blockade of type I IFN signaling starting at day 4 induced dysfunctional CD8+ T cells with depressed cytokine responses and expression of phenotypic markers suggesting exhaustion. Thus, only the later maturation phase of anti-WNV CD8+ T cell development requires type I IFN signaling. WNV infection experiments in BATF3-/- mice, which lack CD8-α dendritic cells and have impaired priming due to inefficient antigen cross-presentation, revealed a similar effect of blocking IFN signaling on CD8+ T cell maturation. Collectively, our results suggest that cell non-autonomous type I IFN signaling shapes maturation of antiviral CD8+ T cell response at a stage distinct from the initial priming event.
Vyšlo v časopise:
A Temporal Role Of Type I Interferon Signaling in CD8 T Cell Maturation during Acute West Nile Virus Infection. PLoS Pathog 7(12): e32767. doi:10.1371/journal.ppat.1002407
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002407
Souhrn
A genetic absence of the common IFN- α/β signaling receptor (IFNAR) in mice is associated with enhanced viral replication and altered adaptive immune responses. However, analysis of IFNAR-/- mice is limited for studying the functions of type I IFN at discrete stages of viral infection. To define the temporal functions of type I IFN signaling in the context of infection by West Nile virus (WNV), we treated mice with MAR1-5A3, a neutralizing, non cell-depleting anti-IFNAR antibody. Inhibition of type I IFN signaling at or before day 2 after infection was associated with markedly enhanced viral burden, whereas treatment at day 4 had substantially less effect on WNV dissemination. While antibody treatment prior to infection resulted in massive expansion of virus-specific CD8+ T cells, blockade of type I IFN signaling starting at day 4 induced dysfunctional CD8+ T cells with depressed cytokine responses and expression of phenotypic markers suggesting exhaustion. Thus, only the later maturation phase of anti-WNV CD8+ T cell development requires type I IFN signaling. WNV infection experiments in BATF3-/- mice, which lack CD8-α dendritic cells and have impaired priming due to inefficient antigen cross-presentation, revealed a similar effect of blocking IFN signaling on CD8+ T cell maturation. Collectively, our results suggest that cell non-autonomous type I IFN signaling shapes maturation of antiviral CD8+ T cell response at a stage distinct from the initial priming event.
Zdroje
1. IsaacsALindenmannJ 1957 Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci 147 258 267
2. StarkGRKerrIMWilliamsBRSilvermanRHSchreiberRD 1998 How cells respond to interferons. Annu Rev Biochem 67 227 264
3. SchogginsJWWilsonSJPanisMMurphyMYJonesCT 2011 A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 472 481 485
4. ColonnaMTrinchieriGLiuYJ 2004 Plasmacytoid dendritic cells in immunity. Nat Immunol 5 1219 1226
5. SamuelMADiamondMS 2006 Pathogenesis of West Nile virus infection: A balance between virulence, innate and adaptive immunity, and viral evasion. J Virol 80 9349 9360
6. DaffisSSutharMSSzretterKJGaleMJrDiamondMS 2009 Induction of IFN-beta and the innate antiviral response in myeloid cells occurs through an IPS-1-dependent signal that does not require IRF-3 and IRF-7. PLoS Pathog 5 e1000607
7. MackenzieJSGublerDJPetersenLR 2004 Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses. Nat Med 10 S98 109
8. SamuelMADiamondMS 2005 Type I IFN protects against lethal West Nile Virus infection by restricting cellular tropism and enhancing neuronal survival. J Virol 79 13350 13361
9. Le BonAToughDF 2002 Links between innate and adaptive immunity via type I interferon. Curr Opin Immunol 14 432 436
10. Hervas-StubbsSPerez-GraciaJLRouzautAFernandez de SanmamedMLe BonA 2011 Direct Effects of type I IFNs on cells of the immune system. Clin Cancer Res 17 2619 2627
11. PurthaWEChachuKAVirginHWDiamondMS 2008 Early B-cell activation after West Nile virus infection requires alpha/beta interferon but not antigen receptor signaling. J Virol 82 10964 10974
12. Le BonASchiavoniGD'AgostinoGGresserIBelardelliF 2001 Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. Immunity 14 461 470
13. Le BonAThompsonCKamphuisEDurandVRossmannC 2006 Cutting edge: enhancement of antibody responses through direct stimulation of B and T cells by type I IFN. J Immunol 176 2074 2078
14. BanchereauJBriereFCauxCDavoustJLebecqueS 2000 Immunobiology of dendritic cells. Annu Rev Immunol 18 767 811
15. KohlmeierJECookenhamTRobertsADMillerSCWoodlandDL 2010 Type I interferons regulate cytolytic activity of memory CD8(+) T cells in the lung airways during respiratory virus challenge. Immunity 33 96 105
16. QuigleyMHuangXYangY 2008 STAT1 signaling in CD8 T cells is required for their clonal expansion and memory formation following viral infection in vivo. J Immunol 180 2158 2164
17. Le BonAEtchartNRossmannCAshtonMHouS 2003 Cross-priming of CD8+ T cells stimulated by virus-induced type I interferon. Nat Immunol 4 1009 1015
18. HildnerKEdelsonBTPurthaWEDiamondMMatsushitaH 2008 Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science 322 1097 1100
19. FrenzTWaiblerZHofmannJHamdorfMLantermannM 2010 Concomitant type I IFN receptor-triggering of T cells and of DC is required to promote maximal modified vaccinia virus Ankara-induced T-cell expansion. Eur J Immunol 40 2769 2777
20. PrinzMSchmidtHMildnerAKnobelochKPHanischUK 2008 Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system. Immunity 28 675 686
21. DetjeCNMeyerTSchmidtHKreuzDRoseJK 2009 Local type I IFN receptor signaling protects against virus spread within the central nervous system. J Immunol 182 2297 2304
22. Le BonADurandVKamphuisEThompsonCBulfone-PausS 2006 Direct stimulation of T cells by type I IFN enhances the CD8+ T cell response during cross-priming. J Immunol 176 4682 4689
23. SheehanKCLaiKSDunnGPBruceATDiamondMS 2006 Blocking monoclonal antibodies specific for mouse IFN-alpha/beta receptor subunit 1 (IFNAR-1) from mice immunized by in vivo hydrodynamic transfection. J Interferon Cytokine Res 26 804 819
24. WherryEJHaSJKaechSMHainingWNSarkarS 2007 Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity 27 670 684
25. SamuelMAWhitbyKKellerBCMarriABarchetW 2006 PKR and RNAse L contribute to protection against lethal West Nile virus infection by controlling early viral spread in the periphery and replication in neurons. J Virol 80 7009 7019
26. DelhayeSPaulSBlakqoriGMinetMWeberF 2006 Neurons produce type I interferon during viral encephalitis. Proc Natl Acad Sci U S A 103 7835 7840
27. KolumamGAThomasSThompsonLJSprentJMurali-KrishnaK 2005 Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection. J Exp Med 202 637 650
28. CoroESChangWLBaumgarthN 2006 Type I IFN receptor signals directly stimulate local B cells early following influenza virus infection. J Immunol 176 4343 4351
29. DiamondMSShresthaBMarriAMahanDEngleM 2003 B cells and antibody play critical roles in the immediate defense of disseminated infection by West Nile encephalitis virus. J Virol 77 2578 2586
30. DiamondMSSitatiEFriendLShresthaBHiggsS 2003 A critical role for induced IgM in the protection against West Nile virus infection. J Exp Med 198 1853 1862
31. ShresthaBDiamondMS 2004 The role of CD8+ T cells in the control of West Nile virus infection. J Virol 78 8312 8321
32. WangYLobigsMLeeEMullbacherA 2003 CD8+ T cells mediate recovery and immunopathology in West Nile virus encephalitis. J Virol 77 13323 13334
33. PurthaWEMyersNMitaksovVSitatiEConnollyJ 2007 Antigen-specific cytotoxic T lymphocytes protect against lethal West Nile virus encephalitis. Eur J Immunol 37 1845 1854
34. BrienJDUhrlaubJLNikolich-ZugichJ 2007 Protective capacity and epitope specificity of CD8(+) T cells responding to lethal West Nile virus infection. Eur J Immunol 37 1855 1863
35. BeasleyDWLiLSudermanMTBarrettAD 2002 Mouse neuroinvasive phenotype of West Nile virus strains varies depending upon virus genotype. Virology 296 17 23
36. KellerBCFredericksenBLSamuelMAMockREMasonPW 2006 Resistance to alpha/beta interferon is a determinant of West Nile virus replication fitness and virulence. J Virol 80 9424 9434
37. DikopoulosNBertolettiAKrogerAHauserHSchirmbeckR 2005 Type I IFN negatively regulates CD8+ T cell responses through IL-10-producing CD4+ T regulatory 1 cells. J Immunol 174 99 109
38. LiuXSXuYHardyLKhammanivongVZhaoW 2003 IL-10 mediates suppression of the CD8 T cell IFN-gamma response to a novel viral epitope in a primed host. J Immunol 171 4765 4772
39. LanteriMCO'BrienKMPurthaWECameronMJLundJM 2009 Tregs control the development of symptomatic West Nile virus infection in humans and mice. J Clin Invest 119 3266 3277
40. LapentaCSantiniSMSpadaMDonatiSUrbaniF 2006 IFN-alpha-conditioned dendritic cells are highly efficient in inducing cross-priming CD8(+) T cells against exogenous viral antigens. Eur J Immunol 36 2046 2060
41. WeiJWaithmanJLataRMifsudNACebonJ 2010 Influenza A infection enhances cross-priming of CD8+ T cells to cell-associated antigens in a TLR7- and type I IFN-dependent fashion. J Immunol 185 6013 6022
42. EdelsonBTKcWJuangRKohyamaMBenoitLA 2010 Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells. J Exp Med 207 823 836
43. EjrnaesMFilippiCMMartinicMMLingEMTogherLM 2006 Resolution of a chronic viral infection after interleukin-10 receptor blockade. J Exp Med 203 2461 2472
44. BrooksDGTrifiloMJEdelmannKHTeytonLMcGavernDB 2006 Interleukin-10 determines viral clearance or persistence in vivo. Nat Med 12 1301 1309
45. WherryEJBlattmanJNMurali-KrishnaKvan der MostRAhmedR 2003 Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol 77 4911 4927
46. ZajacAJBlattmanJNMurali-KrishnaKSourdiveDJSureshM 1998 Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med 188 2205 2213
47. DaffisSLazearHMLiuWJAudsleyMEngleM 2011 The naturally attenuated Kunjin strain of West Nile virus shows enhanced sensitivity to the host type I interferon response. J Virol 85 5664 5668
48. ZietaraNLyszkiewiczMGekaraNPuchalkaJDos SantosVA 2009 Absence of IFN-beta impairs antigen presentation capacity of splenic dendritic cells via down-regulation of heat shock protein 70. J Immunol 183 1099 1109
49. HuberJPFarrarJD 2011 Regulation of effector and memory T-cell functions by type I interferon. Immunology 132 466 474
50. ThompsonLJKolumamGAThomasSMurali-KrishnaK 2006 Innate inflammatory signals induced by various pathogens differentially dictate the IFN-I dependence of CD8 T cells for clonal expansion and memory formation. J Immunol 177 1746 1754
51. KamphuisEJuntTWaiblerZForsterRKalinkeU 2006 Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia. Blood 108 3253 3261
52. CousensLPPetersonRHsuSDornerAAltmanJD 1999 Two roads diverged: interferon alpha/beta- and interleukin 12-mediated pathways in promoting T cell interferon gamma responses during viral infection. J Exp Med 189 1315 1328
53. HarringtonLEGalvanMBaumLGAltmanJDAhmedR 2000 Differentiating between memory and effector CD8 T cells by altered expression of cell surface O-glycans. J Exp Med 191 1241 1246
54. KaechSMTanJTWherryEJKoniecznyBTSurhCD 2003 Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat Immunol 4 1191 1198
55. SarkarSKaliaVHainingWNKoniecznyBTSubramaniamS 2008 Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates. J Exp Med 205 625 640
56. BarberDLWherryEJMasopustDZhuBAllisonJP 2006 Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439 682 687
57. HeathWRCarboneFR 2001 Cross-presentation, dendritic cells, tolerance and immunity. Annu Rev Immunol 19 47 64
58. BennettSRCarboneFRKaramalisFFlavellRAMillerJF 1998 Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 393 478 480
59. XiaoZCaseyKAJamesonSCCurtsingerJMMescherMF 2009 Programming for CD8 T cell memory development requires IL-12 or type I IFN. J Immunol 182 2786 2794
60. ToughDF 2004 Type I interferon as a link between innate and adaptive immunity through dendritic cell stimulation. Leuk Lymphoma 45 257 264
61. KochFStanzlUJenneweinPJankeKHeuflerC 1996 High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10. J Exp Med 184 741 746
62. BrienJDUhrlaubJLHirschAWileyCANikolich-ZugichJ 2009 Key role of T cell defects in age-related vulnerability to West Nile virus. J Exp Med 206 2735 2745
63. EbelGDDupuisAPIIINgoKNicholasDKauffmanE 2001 Partial genetic characterization of West Nile Virus strains, New York State, 2000. Emerg Inf Dis 7 650 653
64. MehlhopEDiamondMS 2006 Protective immune responses against West Nile virus are primed by distinct complement activation pathways. J Exp Med 203 1371 1381
65. TscharkeDCKarupiahGZhouJPalmoreTIrvineKR 2005 Identification of poxvirus CD8+ T cell determinants to enable rational design and characterization of smallpox vaccines. J Exp Med 201 95 104
66. ByersAMKemballCCMoserJMLukacherAE 2003 Cutting edge: rapid in vivo CTL activity by polyoma virus-specific effector and memory CD8+ T cells. J Immunol 171 17 21
67. JellisonERKimSKWelshRM 2005 Cutting edge: MHC class II-restricted killing in vivo during viral infection. J Immunol 174 614 618
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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