#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Unique Type I Interferon Responses Determine the Functional Fate of Migratory Lung Dendritic Cells during Influenza Virus Infection


Migratory lung dendritic cells (DCs) transport viral antigen from the lungs to the draining mediastinal lymph nodes (MLNs) during influenza virus infection to initiate the adaptive immune response. Two major migratory DC subsets, CD103+ DCs and CD11bhigh DCs participate in this function and it is not clear if these antigen presenting cell (APC) populations become directly infected and if so whether their activity is influenced by the infection. In these experiments we show that both subpopulations can become infected and migrate to the draining MLN but a difference in their response to type I interferon (I-IFN) signaling dictates the capacity of the virus to replicate. CD103+ DCs allow the virus to replicate to significantly higher levels than do the CD11bhigh DCs, and they release infectious virus in the MLNs and when cultured ex-vivo. Virus replication in CD11bhigh DCs is inhibited by I-IFNs, since ablation of the I-IFN receptor (IFNAR) signaling permits virus to replicate vigorously and productively in this subset. Interestingly, CD103+ DCs are less sensitive to I-IFNs upregulating interferon-induced genes to a lesser extent than CD11bhigh DCs. The attenuated IFNAR signaling by CD103+ DCs correlates with their described superior antigen presentation capacity for naïve CD8+ T cells when compared to CD11bhigh DCs. Indeed ablation of IFNAR signaling equalizes the competency of the antigen presenting function for the two subpopulations. Thus, antigen presentation by lung DCs is proportional to virus replication and this is tightly constrained by I-IFN. The “interferon-resistant” CD103+ DCs may have evolved to ensure the presentation of viral antigens to T cells in I-IFN rich environments. Conversely, this trait may be exploitable by viral pathogens as a mechanism for systemic dissemination.


Vyšlo v časopise: Unique Type I Interferon Responses Determine the Functional Fate of Migratory Lung Dendritic Cells during Influenza Virus Infection. PLoS Pathog 7(11): e32767. doi:10.1371/journal.ppat.1002345
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002345

Souhrn

Migratory lung dendritic cells (DCs) transport viral antigen from the lungs to the draining mediastinal lymph nodes (MLNs) during influenza virus infection to initiate the adaptive immune response. Two major migratory DC subsets, CD103+ DCs and CD11bhigh DCs participate in this function and it is not clear if these antigen presenting cell (APC) populations become directly infected and if so whether their activity is influenced by the infection. In these experiments we show that both subpopulations can become infected and migrate to the draining MLN but a difference in their response to type I interferon (I-IFN) signaling dictates the capacity of the virus to replicate. CD103+ DCs allow the virus to replicate to significantly higher levels than do the CD11bhigh DCs, and they release infectious virus in the MLNs and when cultured ex-vivo. Virus replication in CD11bhigh DCs is inhibited by I-IFNs, since ablation of the I-IFN receptor (IFNAR) signaling permits virus to replicate vigorously and productively in this subset. Interestingly, CD103+ DCs are less sensitive to I-IFNs upregulating interferon-induced genes to a lesser extent than CD11bhigh DCs. The attenuated IFNAR signaling by CD103+ DCs correlates with their described superior antigen presentation capacity for naïve CD8+ T cells when compared to CD11bhigh DCs. Indeed ablation of IFNAR signaling equalizes the competency of the antigen presenting function for the two subpopulations. Thus, antigen presentation by lung DCs is proportional to virus replication and this is tightly constrained by I-IFN. The “interferon-resistant” CD103+ DCs may have evolved to ensure the presentation of viral antigens to T cells in I-IFN rich environments. Conversely, this trait may be exploitable by viral pathogens as a mechanism for systemic dissemination.


Zdroje

1. PalesePShawML 2007 Orthomyxoviridae: the viruses and their replication. KnipeDMHowleyPM Fields Virology Philadelphia, PA Lippincott Williams & Wilkins 1647 1689

2. WrightPFNeumannGKawaokaY 2007 In Fields Virology, 5th Edition. DMKnipePMHowley Philadelphia, PA Lippincott Williams & Wilkins 1691 1740

3. BanchereauJSteinmanRM 1998 Dendritic cells and the control of immunity. Nature 392 245 252

4. IwasakiA 2007 Mucosal dendritic cells. Annu Rev Immunol 25 381 418

5. SungSSFuSMRoseCEJrGaskinFJuST 2006 A major lung CD103 (alphaE)-beta7 integrin-positive epithelial dendritic cell population expressing Langerin and tight junction proteins. J Immunol 176 2161 2172

6. JakubzickCBogunovicMBonitoAJKuanELMeradM 2008 Lymph-migrating, tissue-derived dendritic cells are minor constituents within steady-state lymph nodes. J Exp Med 205 2839 2850

7. JakubzickCHelftJKaplanTJRandolphGJ 2008 Optimization of methods to study pulmonary dendritic cell migration reveals distinct capacities of DC subsets to acquire soluble versus particulate antigen. J Immunol Methods 337 121 131

8. del RioMLRodriguez-BarbosaJIKremmerEForsterR 2007 CD103- and CD103+ bronchial lymph node dendritic cells are specialized in presenting and cross-presenting innocuous antigen to CD4+ and CD8+ T cells. J Immunol 178 6861 6866

9. BrimnesMKBonifazLSteinmanRMMoranTM 2003 Influenza virus-induced dendritic cell maturation is associated with the induction of strong T cell immunity to a coadministered, normally nonimmunogenic protein. J Exp Med 198 133 144

10. MoltedoBLopezCBPazosMBeckerMIHermeshT 2009 Cutting edge: stealth influenza virus replication precedes the initiation of adaptive immunity. J Immunol 183 3569 3573

11. GeurtsvanKesselCHWillartMAvan RijtLSMuskensFKoolM 2008 Clearance of influenza virus from the lung depends on migratory langerin+CD11b- but not plasmacytoid dendritic cells. J Exp Med 205 1621 1634

12. BelzGTSmithCMKleinertLReadingPBrooksA 2004 Distinct migrating and nonmigrating dendritic cell populations are involved in MHC class I-restricted antigen presentation after lung infection with virus. Proc Natl Acad Sci U S A 101 8670 8675

13. ThomasPGKeatingRHulse-PostDJDohertyPC 2006 Cell-mediated protection in influenza infection. Emerg Infect Dis 12 48 54

14. LawrenceCWReamRMBracialeTJ 2005 Frequency, specificity, and sites of expansion of CD8+ T cells during primary pulmonary influenza virus infection. J Immunol 174 5332 5340

15. KohlmeierJEWoodlandDL 2009 Immunity to respiratory viruses. Annu Rev Immunol 27 61 82

16. SchulmanJLKilbourneED 1963 Experimental Transmission of Influenza Virus Infection in Mice. I. The Period of Transmissibility. J Exp Med 118 257 266

17. LienenklausSCornitescuMZietaraNLyszkiewiczMGekaraN 2009 Novel reporter mouse reveals constitutive and inflammatory expression of IFN-beta in vivo. J Immunol 183 3229 3236

18. StarkGRKerrIMWilliamsBRSilvermanRHSchreiberRD 1998 How cells respond to interferons. Annu Rev Biochem 67 227 264

19. de VeerMJHolkoMFrevelMWalkerEDerS 2001 Functional classification of interferon-stimulated genes identified using microarrays. J Leukoc Biol 69 912 920

20. SchogginsJWWilsonSJPanisMMurphyMYJonesCT 2011 A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 472 481 485

21. BrassALHuangICBenitaYJohnSPKrishnanMN 2009 The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 139 1243 1254

22. Garcia-SastreADurbinRKZhengHPalesePGertnerR 1998 The role of interferon in influenza virus tissue tropism. J Virol 72 8550 8558

23. MordsteinMKochsGDumoutierLRenauldJCPaludanSR 2008 Interferon-lambda contributes to innate immunity of mice against influenza A virus but not against hepatotropic viruses. PLoS Pathog 4 e1000151

24. LuftTPangKCThomasEHertzogPHartDN 1998 Type I IFNs enhance the terminal differentiation of dendritic cells. J Immunol 161 1947 1953

25. GallucciSLolkemaMMatzingerP 1999 Natural adjuvants: endogenous activators of dendritic cells. Nat Med 5 1249 1255

26. LonghiMPTrumpfhellerCIdoyagaJCaskeyMMatosI 2009 Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med 206 1589 1602

27. HermeshTMoltedoBLopezCBMoranTM 2010 Buying Time- The Immune System Determinants of the Incubation Period to Respiratory Viruses. Viruses 2 2541 2558

28. KohlmeierJEWoodlandDL 2010 A call to arms: interferons prepare bone marrow cells to battle peripheral infections. Cell Host Microbe 7 336 337

29. HintzenGOhlLdel RioMLRodriguez-BarbosaJIPabstO 2006 Induction of tolerance to innocuous inhaled antigen relies on a CCR7-dependent dendritic cell-mediated antigen transport to the bronchial lymph node. J Immunol 177 7346 7354

30. ForsterRSchubelABreitfeldDKremmerERenner-MullerI 1999 CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 99 23 33

31. KimTSBracialeTJ 2009 Respiratory dendritic cell subsets differ in their capacity to support the induction of virus-specific cytotoxic CD8+ T cell responses. PLoS One 4 e4204

32. KissenpfennigAHenriSDuboisBLaplace-BuilheCPerrinP 2005 Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity 22 643 654

33. JungSUnutmazDWongPSanoGDe los SantosK 2002 In vivo depletion of CD11c(+) dendritic cells abrogates priming of CD8(+) T cells by exogenous cell-associated antigens. Immunity 17 211 220

34. KlenkHDRottROrlichMBlodornJ 1975 Activation of influenza A viruses by trypsin treatment. Virology 68 426 439

35. WagnerRR 1955 A pantropic strain of influenza virus: generalized infection and viremia in the infant mouse. Virology 1 497 515

36. ChoppinPW 1969 Replication of influenza virus in a continuous cell line: high yield of infective virus from cells inoculated at high multiplicity. Virology 39 130 134

37. SamuelCE 2001 Antiviral actions of interferons. Clin Microbiol Rev 14778 809 table of contents

38. SchmidSMordsteinMKochsGGarcia-SastreATenoeverBR 2010 Transcription factor redundancy ensures induction of the antiviral state. J Biol Chem 285 42013 42022

39. YountJSMoltedoBYangYYCharronGMoranTM 2010 Palmitoylome profiling reveals S-palmitoylation-dependent antiviral activity of IFITM3. Nat Chem Biol 6 610 614

40. HermeshTMoltedoBMoranTMLopezCB 2010 Antiviral instruction of bone marrow leukocytes during respiratory viral infections. Cell Host Microbe 7 343 353

41. OsterlundPVeckmanVSirenJKlucherKMHiscottJ 2005 Gene expression and antiviral activity of alpha/beta interferons and interleukin-29 in virus-infected human myeloid dendritic cells. J Virol 79 9608 9617

42. Phipps-YonasHSetoJSealfonSCMoranTMFernandez-SesmaA 2008 Interferon-beta pretreatment of conventional and plasmacytoid human dendritic cells enhances their activation by influenza virus. PLoS Pathog 4 e1000193

43. GinhouxFLiuKHelftJBogunovicMGreterM 2009 The origin and development of nonlymphoid tissue CD103+ DCs. J Exp Med 206 3115 3130

44. LiuKVictoraGDSchwickertTAGuermonprezPMeredithMM 2009 In vivo analysis of dendritic cell development and homeostasis. Science 324 392 397

45. LandsmanLVarolCJungS 2007 Distinct differentiation potential of blood monocyte subsets in the lung. J Immunol 178 2000 2007

46. JakubzickCTackeFGinhouxFWagersAJvan RooijenN 2008 Blood monocyte subsets differentially give rise to CD103+ and CD103- pulmonary dendritic cell populations. J Immunol 180 3019 3027

47. LiuBMinkSWongKASteinNGetmanC 2004 PIAS1 selectively inhibits interferon-inducible genes and is important in innate immunity. Nat Immunol 5 891 898

48. FennerJEStarrRCornishALZhangJGMetcalfD 2006 Suppressor of cytokine signaling 1 regulates the immune response to infection by a unique inhibition of type I interferon activity. Nat Immunol 7 33 39

49. ShilatifardA 2006 Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu Rev Biochem 75 243 269

50. SkalskyRLCullenBR 2010 Viruses, microRNAs, and host interactions. Annu Rev Microbiol 64 123 141

51. ItoSAnsariPSakatsumeMDickensheetsHVazquezN 1999 Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma- induced genes by suppressing tyrosine phosphorylation of STAT1. Blood 93 1456 1463

52. HelftJGinhouxFBogunovicMMeradM 2010 Origin and functional heterogeneity of non-lymphoid tissue dendritic cells in mice. Immunol Rev 234 55 75

53. DudziakDKamphorstAOHeidkampGFBuchholzVRTrumpfhellerC 2007 Differential antigen processing by dendritic cell subsets in vivo. Science 315 107 111

54. RotzschkeOFalkKDeresKSchildHNordaM 1990 Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature 348 252 254

55. PamerECresswellP 1998 Mechanisms of MHC class I–restricted antigen processing. Annu Rev Immunol 16 323 358

56. RockKLGoldbergAL 1999 Degradation of cell proteins and the generation of MHC class I-presented peptides. Annu Rev Immunol 17 739 779

57. Van BleekGMNathensonSG 1990 Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule. Nature 348 213 216

58. CarboneFRBevanMJ 1990 Class I-restricted processing and presentation of exogenous cell-associated antigen in vivo. J Exp Med 171 377 387

59. SchmolkeMGarcia-SastreA 2010 Evasion of innate and adaptive immune responses by influenza A virus. Cell Microbiol 12 873 880

60. SerbinaNVPamerEG 2006 Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 7 311 317

61. LinKLSuzukiYNakanoHRamsburgEGunnMD 2008 CCR2+ Monocyte-Derived Dendritic Cells and Exudate Macrophages Produce Influenza-Induced Pulmonary Immune Pathology and Mortality. J Immunol 180 2562 2572

62. Le BorgneMEtchartNGoubierALiraSASirardJC 2006 Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8+ T cell crosspriming in vivo. Immunity 24 191 201

63. HuffordMMKimTSSunJBracialeTJ 2011 Antiviral CD8+ T cell effector activities in situ are regulated by target cell type. J Exp Med 208 167 180

64. BeatySRRoseCEJrSungSS 2007 Diverse and potent chemokine production by lung CD11bhigh dendritic cells in homeostasis and in allergic lung inflammation. J Immunol 178 1882 1895

65. EichelbergerMCWangMLAllanWWebsterRGDohertyPC 1991 Influenza virus RNA in the lung and lymphoid tissue of immunologically intact and CD4-depleted mice. J Gen Virol 72 Pt 7 1695 1698

66. Jelley-GibbsDMBrownDMDibbleJPHaynesLEatonSM 2005 Unexpected prolonged presentation of influenza antigens promotes CD4 T cell memory generation. J Exp Med 202 697 706

67. ZammitDJTurnerDLKlonowskiKDLefrancoisLCauleyLS 2006 Residual antigen presentation after influenza virus infection affects CD8 T cell activation and migration. Immunity 24 439 449

68. KimTSHuffordMMSunJFuYXBracialeTJ 2010 Antigen persistence and the control of local T cell memory by migrant respiratory dendritic cells after acute virus infection. J Exp Med 207 1161 1172

69. RomaniNGrunerSBrangDKampgenELenzA 1994 Proliferating dendritic cell progenitors in human blood. J Exp Med 180 83 93

70. SallustoFLanzavecchiaA 1994 Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 179 1109 1118

71. SteinmanRM 2010 Some active areas of DC research and their medical potential. Eur J Immunol 40 2085 2088

72. KimSLeeJBLeeGKChangJ 2009 Vaccination with recombinant adenoviruses and dendritic cells expressing prostate-specific antigens is effective in eliciting CTL and suppresses tumor growth in the experimental prostate cancer. Prostate 69 938 948

73. GilboaEViewegJ 2004 Cancer immunotherapy with mRNA-transfected dendritic cells. Immunol Rev 199 251 263

74. DubskyPSaitoHLeogierMDantinCConnollyJE 2007 IL-15-induced human DC efficiently prime melanoma-specific naive CD8+ T cells to differentiate into CTL. Eur J Immunol 37 1678 1690

75. CarneroELiWBorderiaAVMoltedoBMoranT 2009 Optimization of human immunodeficiency virus gag expression by newcastle disease virus vectors for the induction of potent immune responses. J Virol 83 584 597

76. NiuLTerminiJMKanagaveluSKGuptaSRollandMM 2011 Preclinical evaluation of HIV-1 therapeutic ex vivo dendritic cell vaccines expressing consensus Gag antigens and conserved Gag epitopes. Vaccine 29 2110 2119

77. ShankarEMCheKFMessmerDLifsonJDLarssonM 2011 Expression of a Broad Array of Negative Costimulatory Molecules and Blimp-1 in T Cells following Priming by HIV-1 Pulsed Dendritic Cells. Mol Med 17 229 240

78. CobbARobertsLKPaluckaAKMeadHMontesM 2011 Development of a HIV-1 lipopeptide antigen pulsed therapeutic dendritic cell vaccine. J Immunol Methods 365 27 37

79. MossWJGriffinDE 2006 Global measles elimination. Nat Rev Microbiol 4 900 908

80. ArvinAM 1996 Varicella-zoster virus. Clin Microbiol Rev 9 361 381

81. BeigelJHFarrarJHanAMHaydenFGHyerR 2005 Avian influenza A (H5N1) infection in humans. N Engl J Med 353 1374 1385

82. HogquistKAJamesonSCHeathWRHowardJLBevanMJ 1994 T cell receptor antagonist peptides induce positive selection. Cell 76 17 27

83. van den BroekMFMullerUHuangSAguetMZinkernagelRM 1995 Antiviral defense in mice lacking both alpha/beta and gamma interferon receptors. J Virol 69 4792 4796

84. MullerUSteinhoffUReisLFHemmiSPavlovicJ 1994 Functional role of type I and type II interferons in antiviral defense. Science 264 1918 1921

85. JenkinsMRWebbyRDohertyPCTurnerSJ 2006 Addition of a prominent epitope affects influenza A virus-specific CD8+ T cell immunodominance hierarchies when antigen is limiting. J Immunol 177 2917 2925

86. VermaelenKYCarro-MuinoILambrechtBNPauwelsRA 2001 Specific migratory dendritic cells rapidly transport antigen from the airways to the thoracic lymph nodes. J Exp Med 193 51 60

87. ReedLJMuenchH 1938 A simple method of estimating fifty per cent end points. Am J Hyg 27 493 497

88. YountJSKrausTAHorvathCMMoranTMLopezCB 2006 A novel role for viral-defective interfering particles in enhancing dendritic cell maturation. J Immunol 177 4503 4513

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2011 Číslo 11
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#