WDFY1 mediates TLR3/4 signaling by recruiting TRIF |
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Authors: | Yun-Hong Hu Yu Zhang Li-Qun Jiang Shuai Wang Cao-Qi Lei Ming-Shun Sun Hong-Bing Shu Yu Liu |
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Institution: | State Key Laboratory of Virology, Medical Research Institute, College of Life Sciences, Wuhan University, Wuhan, China |
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Abstract: | Toll-like receptors (TLRs) are pattern recognition receptors that sense a variety of pathogens, initiate innate immune responses, and direct adaptive immunity. All TLRs except TLR3 recruit the adaptor MyD88 to ultimately elicit inflammatory gene expression, whereas TLR3 and internalized TLR4 use TIR-domain-containing adaptor TRIF for the induction of type I interferon and inflammatory cytokines. Here, we identify the WD repeat and FYVE-domain-containing protein WDFY1 as a crucial adaptor protein in the TLR3/4 signaling pathway. Overexpression of WDFY1 potentiates TLR3- and TLR4-mediated activation of NF-κB, interferon regulatory factor 3 (IRF3), and production of type I interferons and inflammatory cytokines. WDFY1 depletion has the opposite effect. WDFY1 interacts with TLR3 and TLR4 and mediates the recruitment of TRIF to these receptors. Our findings suggest a crucial role for WDFY1 in bridging the TLR–TRIF interaction, which is necessary for TLR signaling. |
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Keywords: | signal transduction TLR TRIF WDFY1 |
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