TLR5 functions as a scavenger receptor to enhance flagellin-specific CD4 T cell Responses (136.29)

Abstract Innate immune activation via Toll-like Receptors (TLRs) causes dendritic cell maturation and the production of inflammatory mediators. Our data also demonstrate that TLR5 functions as a scavenger receptor for flagellin, enhancing the activation of flagellin-specific CD4 T cells. Flagellin-specific CD4 T cells were found to expand poorly in TLR5-deficient mice immunized with flagellin and this deficiency persisted even when additional TLR agonists were provided. In marked contrast, TLR5-deficient mice generated a robust flagellin-specific T cell response to processed flagellin peptide. The deficiency in flagellin-specific T cell activation was also detected in TLR5-deficient mice that were orally infected with a flagellated pathogen, demonstrating that TLR5 is responsible for directing a dominant CD4 response to flagellin in the context of infectious disease. Together, these data demonstrate that in addition to its function as an initiator of innate inflammation, TLR5 functions as a scavenger receptor allowing optimal presentation of flagellin epitopes to CD4 T cells.