Rapid CD4+ T-cell responses to bacterial flagellin require dendritic cell expression of Syk and CARD9More about Open Access at the Crick
Authors listShaikh M Atif Seung-Joo Lee Lin-Xi Li Satoshi Uematsu Shizuo Akira Sara Gorjestani Xin Lin Edina Schweighoffer Victor Tybulewicz Stephen J McSorley
Toll-like receptors (TLRs) can recognize microbial patterns and utilize adaptor molecules, such as-MyD88 or (TRIF TIR-domain-containing adapter-inducing interferon-β), to initiate downstream signaling that ultimately affects the initiation of adaptive immunity. In addition to this inflammatory role, TLR5 expression on dendritic cells can favor antigen presentation of flagellin peptides and thus increase the sensitivity of flagellin-specific T-cell responses in vitro and in vivo. Here, we examined the role of alternative signaling pathways that might regulate flagellin antigen presentation in addition to MyD88. These studies suggest a requirement for spleen tyrosine kinase, a noncanonical TLR-signaling adaptor molecule, and its downstream molecule CARD9 in regulating the sensitivity of flagellin-specific CD4(+) T-cell responses in vitro and in vivo. Thus, a previously unappreciated signaling pathway plays an important role in regulating the dominance of flagellin-specific T-cell responses.
Journal European Journal of Immunology
Issue number 2