Figure 7.

Proposed model for Syk and CARD9 involvement in TLR5-mediated flagellin antigen presentation. DCs expressing TLR5 can engage a noncanonical pathway via Syk and CARD9 to enhance flagellin specific T-cell activation. This may be the result of (A) direct signals via TLR5 to the Syk and CARD9 pathway to enhance flagellin processing and MHC class II loading during maturation of the phagosome/lysosome. This enhanced processing results in enhanced TCR ligation, upregulation of IL-2 production, and subsequent T-cell clonal expansion. (B, C) Alternatively, either (B) a Syk/CARD9 pathway may enhance flagellin processing downstream of a TLR5 coreceptor, or (C) Syk and CARD9 activation occurs during flagellin processing in the phago/lysosome, following Syk-independent, TLR5-mediated uptake of flagellin.