ZCCHC3 modulates TLR3-mediated signaling by promoting recruitment of TRIF to TLR3.

ZCCHC3 modulates TLR3-mediated signaling by promoting recruitment of TRIF to TLR3.
J Mol Cell Biol. 2020 Mar 05;:
Authors: Zang R, Lian H, Zhong X, Yang Q, Shu HB
Abstract
Toll-like receptor 3 (TLR3)-mediated signaling is important for host defense against RNA virus. Upon viral RNA stimulation, TIR domain-containing adaptor inducing IFN-β (TRIF) is recruited to TLR3 and then undergoes oligomerization, which is required for the recruitment of downstream molecules to transmit signals. Here we identified ZCCHC3 as a positive regulator of TLR3-mediated signaling. Overexpression of ZCCHC3 promoted transcription of downstream antiviral genes stimulated by the synthetic TLR3 ligand poly(I:C). ZCCHC3-deficiency markedly inhibited TLR3- but not TLR4-mediated induction of type I interferons (IFNs) and proinflammatory cytokines. Zcchc3-/- mice were more resistant to poly(I:C)- but not LPS-induced inflammatory death. Mechanistically, ZCCHC3 promoted recruitment of TRIF to TLR3 after poly(I:C) stimulation. Our findings reveal that ZCCHC3 plays an important role in TLR3-mediated innate immune response by promoting the recruitment of TRIF to TLR3 after ligand stimulation.
PMID: 32133501 [PubMed - as supplied by publisher]

Source: Mol Biol Cell - March 4, 2020 Category: Molecular Biology Authors: Zang R, Lian H, Zhong X, Yang Q, Shu HB Tags: J Mol Cell Biol Source Type: research