Rapid CD4+ T-cell responses to bacterial flagellin require dendritic cell expression of Syk and CARD9

Shaikh M. Atif, Seung Joo Lee, Lin Xi Li, Satoshi Uematsu, Shizuo Akira, Sara Gorjestani, Xin Lin, Edina Schweighoffer, Victor L J Tybulewicz, Stephen J Mcsorley

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)513-524
Number of pages12
JournalEuropean Journal of Immunology
Volume45
Issue number2
DOIs
StatePublished - Feb 1 2015

Keywords

  • Bacterial infection
  • CARD9
  • CD4 T cells
  • Syk
  • TLRs

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Atif, S. M., Lee, S. J., Li, L. X., Uematsu, S., Akira, S., Gorjestani, S., Lin, X., Schweighoffer, E., Tybulewicz, V. L. J., & Mcsorley, S. J. (2015). Rapid CD4+ T-cell responses to bacterial flagellin require dendritic cell expression of Syk and CARD9. European Journal of Immunology, 45(2), 513-524. https://doi.org/10.1002/eji.201444744