Acquisition of Pneumococci Specific Effector and Regulatory Cd4 T Cells Localising within Human Upper Respiratory-Tract Mucosal Lymphoid Tissue
The upper respiratory tract mucosa is the location for commensal Streptococcus (S.) pneumoniae colonization and therefore represents a major site of contact between host and bacteria. The CD4+ T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invasive disease, with data suggesting a critical role for Th17 cells in mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate age-related sequestration of Th1 and Th17 CD4+ T cells reactive to pneumococcal protein antigens within mucosal lymphoid tissue. CD25hi T cell depletion and utilisation of pneumococcal specific MHCII tetramers revealed the presence of antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to suppress these responses. The balance between mucosal effector and regulatory CD4+ T cell immunity is likely to be critical to pneumococcal commensalism and the prevention of unwanted pathology associated with carriage. However, if dysregulated, such responses may render the host more susceptible to invasive pneumococcal infection and adversely affect the successful implementation of both polysaccharide-conjugate and novel protein-based pneumococcal vaccines.
Vyšlo v časopise:
Acquisition of Pneumococci Specific Effector and Regulatory Cd4 T Cells Localising within Human Upper Respiratory-Tract Mucosal Lymphoid Tissue. PLoS Pathog 7(12): e32767. doi:10.1371/journal.ppat.1002396
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002396
Souhrn
The upper respiratory tract mucosa is the location for commensal Streptococcus (S.) pneumoniae colonization and therefore represents a major site of contact between host and bacteria. The CD4+ T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invasive disease, with data suggesting a critical role for Th17 cells in mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate age-related sequestration of Th1 and Th17 CD4+ T cells reactive to pneumococcal protein antigens within mucosal lymphoid tissue. CD25hi T cell depletion and utilisation of pneumococcal specific MHCII tetramers revealed the presence of antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to suppress these responses. The balance between mucosal effector and regulatory CD4+ T cell immunity is likely to be critical to pneumococcal commensalism and the prevention of unwanted pathology associated with carriage. However, if dysregulated, such responses may render the host more susceptible to invasive pneumococcal infection and adversely affect the successful implementation of both polysaccharide-conjugate and novel protein-based pneumococcal vaccines.
Zdroje
1. 1998 WHO meeting on maternal and neonatal pneumococcal immunization. Wkly Epidemiol Rec 73 187 188 No authors listed
2. MulhollandEKAdegbolaRA 2005 Bacterial infections—a major cause of death among children in Africa. N Eng J Med 352 75 77
3. RudanITomaskovicLBoschi-PintoCCampbellH 2004 on behalf of WHO Child Health Epidemiology Reference Group. Global estimate of the incidence of clinical pneumonia among children under five years of age. Bull World Health Organ 82 891 970
4. HussainMMelegaroAPebodyRGGeorgeREdmundsWJ 2005 A longitudinal household study of Streptococcus pneumoniae nasopharyngeal carriage in a UK setting. Epidemiol Infect 133 891 898
5. ObaroSKAdegbolaRABanyaWAGreenwoodBM 1996 Carriage of pneumococci after pneumococcal vaccination. Lancet 348 271 272
6. LipsitchMWhitneyCGZellEKaijalainenTDaganR 2005 Are anticapsular antibodies the primary mechanism of protection against invasive pneumococcal disease? PLoS Med 2 e15
7. RobinsonKABaughmanWRothrockGBarrettNLPassM 2001 Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995–1998: Opportunities for prevention in the conjugate vaccine era. JAMA 285 1729 1735
8. HillPCAkisanyaASankarehKCheungYBSaakaM 2006 Nasopharyngeal carriage of Streptococcus pneumoniae in Gambian villagers. Clin Infect Dis 43 673 679
9. MusherDMGrooverJERowlandJMWatsonDAStruewingJB 1993 Antibody to capsular polysaccharides of Streptococcus pneumoniae Prevalence, persistence, and response to revaccination. Clin Infect Dis 17 66 73
10. RapolaSJänttiVHaikalaRSyrjänenRCarloneGM 2000 Natural Development of Antibodies to Pneumococcal Surface Protein A, Pneumococcal Surface Adhesin A, and Pneumolysin in Relation to Pneumococcal Carriage and Acute Otitis Media. J Infect Dis 182 1146 1152
11. ZhangZClarkeTBWeiserJN 2009 Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. J Clin Invest 119 1899 1909
12. MalleyRTrzcinskiKSrivastavaAThompson CMAnderson PW 2005 CD4+ T cells mediate antibody-independent acquired immunity to pneumococcal colonization. Proc Natl Acad Sci U S A 102 4848 4853
13. ZhangQBagradeLBernatonieneJClarkeEPatonJC 2007 Low CD4 T cell immunity to pneumolysin is associated with nasopharyngeal carriage of pneumococci in children. J Infect Dis 195 1194 1202
14. LuYJGrossJBogaertDFinnABagradeL 2008 Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathog 4 e1000159
15. MureithiMWFinnAOtaMOZhangQDavenportV 2009 T cell memory response to pneumococcal protein antigens in an area of high pneumococcal carriage and disease. J Infect Dis 200 783 93
16. MalleyR 2010 Antibody and cell-mediated immunity to Streptococcus pneumoniae: implications for vaccine development. J Mol Med 88 135 42
17. van KempenMJRijkersGTVan CauwenbergePB 2000 The immune response in adenoids and tonsils. Int Arch Allergy Immunol 122 8 19
18. AustrianR 1986 Some aspects of the pneumococcal carrier state. J Antimicrob Chemother 18 35 45
19. PatonJCLockRALeeCJLiJPBerryAM 1991 Purification and immunogenicity of genetically obtained pneumolysin toxoids and their conjugation to Streptococcus pneumoniae type 19F polysaccharide. Infect Immun 59 2297 2304
20. DavenportVGrovesEHobbsCGWilliamsNAHeydermanRS 2007 Regulation of Th-1 T cell-dominated immunity to Neisseria meningitidis within the human mucosa. Cell Microbiol 9 1050 1061
21. MylesPRMcKeeverTMPogsonZSmithCJHubbardRB 2009 The incidence of pneumonia using data from a computerized general practice database. Epidemiol Infect 137 709 716
22. OldenhoveGde HeuschMUrbain-VansantenGUrbainJMaliszewskiC 2003 CD4+ CD25+ regulatory T cells control T helper cell type 1 responses to foreign antigens induced by mature dendritic cells in vivo. J Exp Med 198 259 266
23. HoriSCarvalhoTLDemengeotJ 2002 CD25+CD4+ regulatory T cells suppress CD4+ T cell-mediated pulmonary hyperinflammation driven by Pneumocystis carinii in immunodeficient mice. Eur J Immunol 32 1282 91
24. ZhangXIziksonLLiuLWeinerHL 2001 Activation of CD25(+)CD4(+) regulatory T cells by oral antigen administration. J Immunol 167 4245 4253
25. SakaguchiSSakaguchiNAsanoMItohMTodaM 1995 Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155 1151 1164
26. HaraMKingsleyCINiimiMReadSTurveySE 2001 IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo. J Immunol 166 3789 3796
27. O'MahonyCScullyPO'MahonyDMurphySO'BrienF 2008 Commensal-Induced Regulatory T Cells Mediate Protection against Pathogen-Stimulated NF-κB Activation. PLoS Pathogens 4 e1000112
28. StoopJNvan der MolenRGBaanCCvan der LaanLJKuipersEJ 2005 Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. Hepatology 41 771 8
29. WeissLDonkova-PetriniVCaccavelliLBalboMCarbonneilC 2004 Human immunodeficiency virus-driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients. Blood 104 3249 3256
30. FariaAMWeinerHL 2005 Oral tolerance. Immunol Rev 206 232 259
31. SakaguchiSMiyaraMCostantinoCMHaflerDA 2010 FOXP3+ regulatory T cells in the human immune system. Nat Revs Immunol 10 490 500
32. StraussLBergmannCSzczepanskiMGoodingWJohnsonJT 2007 A unique subset of CD4+CD25highFoxp3++ T cells secreting interleukin-10 and transforming growth factor-β1 mediates suppression in the tumor microenvironment. Clin Cancer Res 13 4345 4354
33. TakahashiTTagamiTYamazakiSUedeTShimizuJ 2000 Immunologic self-tolerance maintained by CD25+CD4+ regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 192 303 310
34. ReadSGreenwaldRIzcueARobinsonNMandelbrotD 2006 Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo. J Immunol 177 4376 4383
35. BelkaidYBlanRBSuffiI 2006 Natural regulatory T cells and parasites: a common quest for host homeostasis. Immunol Rev 212 287 300
36. SandnerSEClarksonMRSalamaADSanchez-FueyoADomenigC 2005 Role of the programmed death-1 pathway in regulation of alloimmune responses in vivo. J Immunol 174 3408 3415
37. WongRMScotlandRRLauRLWangCKormanAJ 2007 Programmed death-1 blockade enhances expansion and functional capacity of human melanoma antigen-specific CTLs. Int Immunol 19 1223 1234
38. LaughlinEMMillerJDJamesEFillosDIbegbuCC 2007 Antigen-Specific CD4+ T Cells Recognize Epitopes of Protective Antigen following Vaccination with an Anthrax Vaccine. Infect Immun 75 1852 1860
39. JokinenCHeiskanenLJuvonenHKallinenSKarkolaK 1993 Incidence of community-acquired pneumonia in the population of four municipalities in Eastern Finland. Am J Epidemiol 137 977 988
40. FoyHMConneyMKAllanI 1979 Rates of pneumonia during influenza epidemics in Seattle, 1964 to 1975. J Am Med Assoc 241 253 258
41. LaineCMwangiTThompsonCMObieroJLipsitchM 2004 Age-specific immunoglobulin g (IgG) and IgA to pneumococcal protein antigens in a population in coastal Kenya. Infect Immun 72 3331 3335
42. RoundJLMazmanianSK 2010 Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U S A 107 12204 12209
43. LivingstonMLoachDWilsonMTannockGWBairdM 2010 Gut commensal Lactobacillus reuteri 100-23 stimulates an immunoregulatory response to L. reuteri. Immunol Cell Biol 88 99 102
44. ChristensenHMayMBowenLHickmanMTrotterCL 2010 Meningococcal carriage by age: a systematic review and meta-analysis. Lancet Infect Dis 10 853 861
45. BogaertDvan BelkumASluijterMLuijendijkAde GrootR 2004 Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. The Lancet 363 1871 1872
46. ZhangQLeongSCMcNamaraPSMubarakAMalleyR 2011 Characterisation of Regulatory T Cells in Nasal Associated Lymphoid Tissue in Children: Relationships with Pneumococcal Colonization. PLoS Pathog 7 e1002175 doi:10.1371/journal.ppat.1002175
47. WingKOnishiYPrieto-MartinPYamaguchiTMiyaraM 2008 CTLA-4 Control over Foxp3+ Regulatory T Cell Function. Science 322 271 275
48. ButteMJKeirMEPhamduyTBSharpeAHFreemanGJ 2007 Programmed Death-1 Ligand 1 Interacts Specifically with the B7-1 Costimulatory Molecule to Inhibit T Cell Responses. Immunity 27 111 122
49. QuigleyMPereyraFNilssonBPorichisFFonsecaC 2010 Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF. Nat Med 16 1147 51
50. PaustSLuLMcCartyNCantorH 2004 Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc Natl Acad Sci U S A 101 10398 10403
51. IikuniNLourençoEVHahnBHLa CavaA 2009 Cutting edge: Regulatory T cells directly suppress B cells in systemic lupus erythematosus. J Immunol 183 1518 22
52. CongYFengTFujihashiKSchoebTRElsonCO 2009 A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota. Proc Natl Acad Sci U S A 106 19256 19261
53. LimHWHillsamerPBanhamAHKimCH 2005 Cutting Edge: Direct Suppression of B Cells by CD4+CD25+ Regulatory T Cells. J Immunol 175 4180 4183
54. CromeSQCliveBWangAYKangCYChowV 2010 Inflammatory Effects of Ex Vivo Human Th17 Cells Are Suppressed by Regulatory T Cells. J Immunol 85 3199 3208
55. ReynoldsADStoneDKHutterJABennerEJMosleyRL 2010 Regulatory T Cells Attenuate Th17 Cell-Mediated Nigrostriatal Dopaminergic Neurodegeneration in a Model of Parkinson’s disease. J Immunol 184 2261 2271
56. ZhangQBernatonieneJBagradeLPollardAJMitchellTJ 2006 Serum and mucosal antibody responses to pneumococcal protein antigens in children: relationships with carriage status. Eur J Immunol 36 46 57
57. SturnioloTBonoEDingJRaddrizzaniLTuereciO 1999 Generation of tissue-specific and promiscuous HLA ligand databases using DNA microarrays and virtual HLA class II matrices. Nat Biotechnol 17 555 61
58. NovakEJLiuAWNepomGTKwokWK 1999 MHC class II tetramers identify peptide-specific human CD4+ T cells proliferating in response to influenza A antigen. J Clin Invest 104 R63 R6
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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