TLR2 engagement on CD4(+) T cells enhances effector functions and protective responses to Mycobacterium tuberculosis.
We have previously demonstrated that mycobacterial lipoproteins engage TLR2 on human CD4(+) T cells and upregulate TCR-triggered IFN-γ secretion and cell proliferation in vitro. Here we examined the role of CD4(+) T-cell-expressed TLR2 in Mycobacterium tuberculosis (MTB) Ag-specific T-cell priming and in protection against MTB infection in vivo. Like their human counterparts, mouse CD4(+) T cells express TLR2 and respond to TLR2 costimulation in vitro. This Th1-like response was observed in the context of both polyclonal and Ag-specific TCR stimulation. To evaluate the role of T-cell TLR2 in priming of CD4(+) T cells in vivo, naive MTB Ag85B-specific TCR transgenic CD4(+) T cells (P25 TCR-Tg) were adoptively transferred into Tlr2(-/-) recipient C57BL/6 mice that were then immunized with Ag85B and with or without TLR2 ligand Pam3 Cys-SKKKK. TLR2 engagement during priming resulted in increased numbers of IFN-γ-secreting P25 TCR-Tg T cells 1 week after immunization. P25 TCR-Tg T cells stimulated in vitro via TCR and TLR2 conferred more protection than T cells stimulated via TCR alone when adoptively transferred before MTB infection. Our findings indicate that TLR2 engagement on CD4(+) T cells increases MTB Ag-specific responses and may contribute to protection against MTB infection.
Department of Medicine, Case Western Reserve University, University Hospitals, Cleveland, OH, USA.
Scott M
SM
Reba
Qing
Q
Li
Sophia
S
Onwuzulike
Xuedong
X
Ding
Ahmad F
AF
Karim
Yeritza
Y
Hernandez
Scott A
SA
Fulton
Clifford V
CV
Harding
Christina L
CL
Lancioni
Nancy
N
Nagy
Myriam E
ME
Rodriguez
Pamela A
PA
Wearsch
Roxana E
RE
Rojas
D000217:Acyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000090266:Chromobox Protein Homolog 5; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C000715594:CBX5 protein, human; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D000090266:Chromobox Protein Homolog 5; D007371:Interferon-gamma; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis
CD4+ T cells; Mycobacterium tuberculosis; Toll-like receptor 2