Temporal Expression of Bacterial Proteins Instructs Host CD4 T Cell Expansion and Th17 Development

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Pathogens can substantially alter gene expression within an infected host depending on metabolic or virulence requirements in different tissues, however, the effect of these alterations on host immunity are unclear. Here we visualized multiple CD4 T cell responses to temporally expressed proteins in Salmonella-infected mice. Flagellin-specific CD4 T cells expanded and contracted early, differentiated into Th1 and Th17 lineages, and were enriched in mucosal tissues after oral infection. In contrast, CD4 T cells responding to Salmonella Type-III Secretion System (TTSS) effectors steadily accumulated until bacterial clearance was achieved, primarily differentiated into Th1 cells, and were predominantly detected in systemic tissues. Thus, pathogen regulation of antigen expression plays a major role in orchestrating the expansion, differentiation, and location of antigen-specific CD4 T cells in vivo.

Vyšlo v časopise: Temporal Expression of Bacterial Proteins Instructs Host CD4 T Cell Expansion and Th17 Development. PLoS Pathog 8(1): e32767. doi:10.1371/journal.ppat.1002499
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002499

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1. BarouchDHKorberB 2010 HIV-1 vaccine development after STEP. Annu Rev Med 61 153 167

2. CoffmanRLSherASederRA 2010 Vaccine adjuvants: putting innate immunity to work. Immunity 33 492 503

3. JenkinsMKChuHHMcLachlanJBMoonJJ 2010 On the composition of the preimmune repertoire of T cells specific for Peptide-major histocompatibility complex ligands. Annu Rev Immunol 28 275 294

4. JamesonSCMasopustD 2009 Diversity in T cell memory: an embarrassment of riches. Immunity 31 859 871

5. WeaverCTHattonRDManganPRHarringtonLE 2007 IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol 25 821 852

6. SallustoFLanzavecchiaAArakiKAhmedR 2010 From vaccines to memory and back. Immunity 33 451 463

7. O'SheaJJPaulWE 2010 Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 327 1098 1102

8. SzaboSJKimSTCostaGLZhangXFathmanCG 2000 A novel transcription factor, T-bet directs Th1 lineage commitment. Cell 100 655 669

9. RavindranRFoleyJStoklasekTGlimcherLHMcSorleySJ 2005 Expression of T-bet by CD4 T cells is essential for resistance to Salmonella infection. J Immunol 175 4603 4610

10. ZhouMOuyangW 2003 The function role of GATA-3 in Th1 and Th2 differentiation. Immunol Res 28 25 37

11. MaizelsRMPearceEJArtisDYazdanbakhshMWynnTA 2009 Regulation of pathogenesis and immunity in helminth infections. J Exp Med 206 2059 2066

12. KhaderSAGaffenSLKollsJK 2009 Th17 cells at the crossroads of innate and adaptive immunity against infectious diseases at the mucosa. Mucosal Immunol 2 403 411

13. McSorleySJAschSCostalongaMRieinhardtRLJenkinsMK 2002 Tracking Salmonella-specific CD4 T cells in vivo reveals a local mucosal response to a disseminated infection. Immunity 16 365 377

14. RomanEMillerEHarmsenAWileyJVon AndrianUH 2002 CD4 effector T cell subsets in the response to influenza: heterogeneity, migration, and function. J Exp Med 196 957 968

15. RoanNRGierahnTMHigginsDEStarnbachMN 2006 Monitoring the T cell response to genital tract infection. Proc Natl Acad Sci U S A 103 12069 12074

16. BlairDALefrancoisL 2007 Increased competition for antigen during priming negatively impacts the generation of memory CD4 T cells. Proc Natl Acad Sci U S A 104 15045 15050

17. SrinivasanAMcSorleySJ 2007 Pivotal advance: exposure to LPS suppresses CD4+ T cell cytokine production in Salmonella-infected mice and exacerbates murine typhoid. J Leukoc Biol 81 403 411

18. ReileyWWCalayagMDWittmerSTHuntingtonJLPearlJE 2008 ESAT-6-specific CD4 T cell responses to aerosol Mycobacterium tuberculosis infection are initiated in the mediastinal lymph nodes. Proc Natl Acad Sci U S A 105 10961 10966

19. WolfAJDesvignesLLinasBBanaieeNTamuraT 2008 Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs. J Exp Med 205 105 115

20. MarzoALKlonowskiKDLe BonABorrowPToughDF 2005 Initial T cell frequency dictates memory CD8+ T cell lineage commitment. Nat Immunol 6 793 799

21. HatayeJMoonJJKhorutsAReillyCJenkinsMK 2006 Naive and memory CD4+ T cell survival controlled by clonal abundance. Science 312 114 116

22. BadovinacVPHaringJSHartyJT 2007 Initial T cell receptor transgenic cell precursor frequency dictates critical aspects of the CD8(+) T cell response to infection. Immunity 26 827 841

23. MoonJJChuHHPepperMMcSorleySJJamesonSC 2007 Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. Immunity 27 203 213

24. PepperMLinehanJLPaganAJZellTDileepanT 2010 Different routes of bacterial infection induce long-lived TH1 memory cells and short-lived TH17 cells. Nat Immunol 11 83 89

25. TalaatAMLyonsRHowardSTJohnstonSA 2004 The temporal expression profile of Mycobacterium tuberculosis infection in mice. Proc Natl Acad Sci U S A 101 4602 4607

26. JansenAYuJ 2006 Differential gene expression of pathogens inside infected hosts. Curr Opin Microbiol 9 138 142

27. McSorleySJCooksonBTJenkinsMK 2000 Characterization of CD4+ T cell responses during natural infection with Salmonella typhimurium. J Immunol 164 986 993

28. BergmanMACummingsLAAlanizRCMayedaLFellnerovaI 2005 CD4+-T-cell responses generated during murine Salmonella enterica serovar Typhimurium infection are directed towards multiple epitopes within the natural antigen FliC. Infect Immun 73 7226 7235

29. MoonJJMcSorleySJ 2009 Tracking the dynamics of salmonella specific T cell responses. Curr Top Microbiol Immunol 334 179 198

30. Salazar-GonzalezRMMcSorleySJ 2005 Salmonella flagellin, a microbial target of the innate and adaptive immune system. Immunol Lett 101 117 122

31. LetranSELeeSJAtifSMUematsuSAkiraS 2011 TLR5 functions as an endocytic receptor to enhance flagellin-specific adaptive immunity. Eur J Immunol 41 29 38

32. CummingsLAWilkersonWDBergsbakenTCooksonBT 2006 In vivo, fliC expression by Salmonella enterica serovar Typhimurium is heterogeneous, regulated by ClpX, and anatomically restricted. Mol Microbiol 61 795 809

33. ZhuYRudenskyAYCorperALTeytonLWilsonIA 2003 Crystal structure of MHC class II I-Ab in complex with a human CLIP peptide: prediction of an I-Ab peptide-binding motif. J Mol Biol 326 1157 1174

34. LawleyTDChanKThompsonLJKimCCGovoniGR 2006 Genome-wide screen for Salmonella genes required for long-term systemic infection of the mouse. PLoS Pathog 2 e11

35. AbrahamsGLHenselM 2006 Manipulating cellular transport and immune responses: dynamic interactions between intracellular Salmonella enterica and its host cells. Cell Microbiol 8 728 737

36. MoonJJChuHHHatayeJPaganAJPepperM 2009 Tracking epitope-specific T cells. Nat Protoc 4 565 581

37. GriffinAJMcSorleySJ 2011 Generation of Salmonella-specific Th1 cells requires sustained antigen stimulation. Vaccine 29 2697 2704

38. Salazar-GonzalezRMSrinivasanAGriffinAMuralimohanGErteltJM 2007 Salmonella flagellin induces bystander activation of splenic dendritic cells and hinders bacterial replication in vivo. J Immunol 179 6169 6175

39. SrinivasanASalazar-GonzalezRMJarchoMSandauMMLefrancoisL 2007 Innate immune activation of CD4 T cells in salmonella-infected mice is dependent on IL-18. J Immunol 178 6342 6349

40. Salazar-GonzalezRMNiessJHZammitDJRavindranRSrinivasanA 2006 CCR6-mediated dendritic cell activation of pathogen-specific T cells in Peyer's patches. Immunity 24 623 632

41. BobatSFlores-LangaricaAHitchcockJMarshallJLKingsleyRA 2011 Soluble flagellin, FliC, induces an Ag-specific Th2 response, yet promotes T-bet-regulated Th1 clearance of Salmonella typhimurium infection. Eur J Immunol 41 1606 1618

42. ErikssonSLucchiniSThompsonARhenMHintonJC 2003 Unravelling the biology of macrophage infection by gene expression profiling of intracellular Salmonella enterica. Mol Microbiol 47 103 118

43. BoldTDBanaeiNWolfAJErnstJD 2011 Suboptimal activation of antigen-specific CD4+ effector cells enables persistence of M. tuberculosis in vivo. PLoS Pathog 7 e1002063

44. EgenJGRothfuchsAGFengCGHorwitzMASherA 2011 Intravital imaging reveals limited antigen presentation and T cell effector function in mycobacterial granulomas. Immunity 34 807 819

45. ObstRvan SantenHMMathisDBenoistC 2005 Antigen persistence is required throughout the expansion phase of a CD4(+) T cell response. J Exp Med 201 1555 1565

46. ObstRvan SantenHMMelamedRKamphorstAOBenoistC 2007 Sustained antigen presentation can promote an immunogenic T cell response, like dendritic cell activation. Proc Natl Acad Sci U S A 104 15460 15465

47. GriffinAJMcSorleySJ 2011 Development of protective immunity to Salmonella, a mucosal pathogen with a systemic agenda. Mucosal Immunol 4 371 382

48. UrdahlKBShafianiSErnstJD 2011 Initiation and regulation of T-cell responses in tuberculosis. Mucosal Immunol 4 288 293

49. RaffatelluMSantosRLVerhoevenDEGeorgeMDWilsonRP 2008 Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med 14 421 428

50. ValdezYDiehlGEVallanceBAGrasslGAGuttmanJA 2008 Nramp1 expression by dendritic cells modulates inflammatory responses during Salmonella Typhimurium infection. Cell Microbiol 10 1646 1661

51. Eaves-PylesTMurthyKLiaudetLViragLRossG 2001 Flagellin, a novel mediator of Salmonella-induced epithelial activation and systemic inflammation: I kappa B alpha degradation, induction of nitric oxide synthase, induction of proinflammatory mediators, and cardiovascular dysfunction. J Immunol 166 1248 1260

52. PeckAMellinsED 2010 Precarious balance: Th17 cells in host defense. Infect Immun 78 32 38

53. Richter-DahlforsABuchanAMJFinlayBB 1997 Murine Salmonellosis studied by confocal microscopy: Salmonella typhimurium resides intracellularly inside macrophages and exerts a cytotoxic effect on phagocytes in vivo. J Exp Med 186 569 580

54. GriffinABaraho-HassanDMcSorleySJ 2009 Successful treatment of bacterial infection hinders development of acquired immunity. J Immunol 183 1263 1270

55. BordnerAJ 2010 Towards universal structure-based prediction of class II MHC epitopes for diverse allotypes. PloS One 5 e14383

56. EddySR 2004 What is a hidden Markov model? Nat Biotechnol 22 1315 1316

57. GroismanEAKayserJSonciniFC 1997 Regulation of polymyxin resistance and adaptation to low-Mg2+ environments. J Bacteriol 179 7040 7045

58. WinterSEWinterMGGodinezIYangHJRussmannH 2010 A rapid change in virulence gene expression during the transition from the intestinal lumen into tissue promotes systemic dissemination of Salmonella. PLoS Pathog 6 e1001060

59. BarmanMUnoldDShifleyKAmirEHungK 2008 Enteric salmonellosis disrupts the microbial ecology of the murine gastrointestinal tract. Infect Immun 76 907 915

60. MasopustDVezysVMarzoALLefrancoisL 2001 Preferential localization of effector memory cells in nonlymphoid tissue. Science 291 2413 2417