Affordable Access

deepdyve-link
Publisher Website

Sox4 represses host innate immunity to facilitate pathogen infection by hijacking the TLR signaling networks

Authors
  • Shang, Jian1
  • Zheng, Yuan2
  • Mo, Jiayin2
  • Wang, Wenbiao1
  • Luo, Zhen1
  • Li, Yongkui1
  • Chen, Xulin1
  • Zhang, Qiwei1
  • Wu, Kailang2
  • Liu, Weiyong1
  • Wu, Jianguo1, 2
  • 1 Institute of Medical Microbiology, Jinan University, China , (China)
  • 2 College of Life Sciences, Wuhan University, China , (China)
Type
Published Article
Journal
Virulence
Publisher
Landes Bioscience
Publication Date
Feb 16, 2021
Volume
12
Issue
1
Pages
704–722
Identifiers
DOI: 10.1080/21505594.2021.1882775
PMID: 33517839
PMCID: PMC7894441
Source
PubMed Central
Keywords
Disciplines
  • Research Paper
License
Unknown

Abstract

Toll-like receptors (TLRs) are essential for the protection of the host from pathogen infections by initiating the integration of contextual cues to regulate inflammation and immunity. However, without tightly controlled immune responses, the host will be subjected to detrimental outcomes. Therefore, it is important to balance the positive and negative regulations of TLRs to eliminate pathogen infection, yet avert harmful immunological consequences. This study revealed a distinct mechanism underlying the regulation of the TLR network. The expression of sex-determining region Y-box 4 (Sox4) is induced by virus infection in viral infected patients and cultured cells, which subsequently represses the TLR signaling network to facilitate viral replication at multiple levels by a distinct mechanism. Briefly, Sox4 inhibits the production of myeloid differentiation primary response gene 88 (MyD88) and most of the TLRs by binding to their promoters to attenuate gene transcription. In addition, Sox4 blocks the activities of the TLR/MyD88/IRAK4/TAK1 and TLR/TRIF/TRAF3/TBK1 pathways by repressing their key components. Moreover, Sox4 represses the activation of the nuclear factor kappa-B (NF-κB) through interacting with IKKα/α, and attenuates NF-kB and IFN regulatory factors 3/7 (IRF3/7) abundances by promoting protein degradation. All these contributed to the down-regulation of interferons (IFNs) and IFN-stimulated gene (ISG) expression, leading to facilitate the viral replications. Therefore, we reveal a distinct mechanism by which viral pathogens evade host innate immunity and discover a key regulator in host defense.

Report this publication

Statistics

Seen <100 times