TLR5 functions as an endocytic receptor to enhance flagellin-specific adaptive immunity

Shirdi E. Letran, Seung Joo Lee, Shaikh M. Atif, Satoshi Uematsu, Shizuo Akira, Stephen J Mcsorley

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Innate immune activation via TLR induces dendritic cell maturation and secretion of inflammatory mediators, generating favorable conditions for naïve T-cell activation. Here, we demonstrate a previously unknown function for TLR5, namely that it enhances MHC class-II presentation of flagellin epitopes to CD4+ T cells and is required for induction of robust flagellin-specific adaptive immune responses. Flagellin-specific CD4+ T cells expanded poorly in TLR5-deficient mice immunized with flagellin, a deficiency that persisted even when additional TLR agonists were provided. Flagellin-specific IgG responses were similarly depressed in the absence of TLR5. In marked contrast, TLR5-deficient mice developed robust flagellin-specific T-cell responses when immunized with processed flagellin peptide. Surprisingly, the adaptor molecule Myd88 was not required for robust CD4+ T-cell responses to flagellin, indicating that TLR5 enhances flagellin-specific CD4+ T-cell responses in the absence of conventional TLR signaling. A requirement for TLR5 in generating flagellin-specific CD4+ T-cell activation was also observed when using an in vitro dendritic cell culture system. Together, these data uncover an Myd88-independent function for dendritic cell TLR5 in enhancing the presentation of peptides to flagellin-specific CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)29-38
Number of pages10
JournalEuropean Journal of Immunology
Issue number1
StatePublished - Jan 2011
Externally publishedYes


  • CD4 T cells
  • Dendritic cells
  • TLR

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy


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