First Author | Vasilevsky S | Year | 2008 |
Journal | Eur J Immunol | Volume | 38 |
Issue | 12 | Pages | 3316-26 |
PubMed ID | 19003933 | Mgi Jnum | J:141394 |
Mgi Id | MGI:3818208 | Doi | 10.1002/eji.200838484 |
Citation | Vasilevsky S, et al. (2008) 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. Eur J Immunol 38(12):3316-3326 |
abstractText | 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 naive 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. |