B and CD4+ T-cell expression of TLR2 is critical for optimal induction of a T-cell-dependent humoral immune response to intact Streptococcus pneumoniae.
TLR2(-/-) mice immunized with Streptococcus pneumoniae (Pn) elicit normal IgM, but defective CD4(+) T-cell-dependent type 1 IgG isotype production, associated with a largely intact innate immune response. We studied the T-cell-dependent phosphorylcholine (PC)-specific IgG3 versus the T-cell-independent IgM response to Pn to determine whether TLR2 signals directly via the adaptive immune system. Pn-activated TLR2(-/-) BMDC have only a modest defect in cytokine secretion, undergo normal maturation, and when transferred into naïve WT mice elicit a normal IgM and IgG3 anti-PC response, relative to WT BMDC. Pn synergizes with BCR and TCR signaling for DNA synthesis in purified WT B and CD4(+)T cells, respectively, but is defective in cells lacking TLR2. Pn primes TLR2(-/-) mice for a normal CD4(+) T-cell IFN-gamma recall response. Notably, TLR2(-/-) B cells transferred into RAG-2(-/-) mice with WT CD4(+)T cells, or TLR2(-/-) CD4(+)T cells transferred into athymic nude mice, each elicit a defective IgG3, in contrast to normal IgM, anti-PC response relative to WT cells. These data are the first to demonstrate a major role for B-cell and CD4(+) T-cell expression of TLR2 for eliciting an anti-bacterial humoral immune response.
Vasilevsky
Sam
S
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Chattopadhyay
Gouri
G
Colino
Jesus
J
Yeh
Tze-Jou
TJ
Chen
Quanyi
Q
Sen
Goutam
G
Snapper
Clifford M
CM
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D010641:Phenotype; D013296:Streptococcus pneumoniae / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D007074:Immunoglobulin G; D007075:Immunoglobulin M; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D007371:Interferon-gamma