| Literature DB >> 31110366 |
Lin Wang1, Zhonghua Liu1, Jie Wang1, Haipeng Liu1,2, Juehui Wu1,3, Tianqi Tang1,3, Haohao Li1,3, Hua Yang1, Lianhua Qin1, Dapeng Ma1,2, Jianxia Chen1,2, Feng Liu1, Peng Wang1,3, Ruijuan Zheng1, Peng Song3, Yilong Zhou3, Zhenling Cui1, Xiangyang Wu1,3, Xiaochen Huang1, Haijiao Liang1,3, Shanshan Zhang3, Jingjing Cao3, Chunyan Wu4, Yiping Chen5, Dan Su5, Xinchun Chen6, Gucheng Zeng7, Baoxue Ge8,9,10.
Abstract
Mycobacterium tuberculosis (Mtb)-derived components are usually recognized by pattern recognition receptors to initiate a cascade of innate immune responses. One striking characteristic of Mtb is their utilization of different type VII secretion systems to secrete numerous proteins across their hydrophobic and highly impermeable cell walls, but whether and how these Mtb-secreted proteins are sensed by host immune system remains largely unknown. Here, we report that MPT53 (Rv2878c), a secreted disulfide-bond-forming-like protein of Mtb, directly interacts with TGF-β-activated kinase 1 (TAK1) and activates TAK1 in a TLR2- or MyD88-independent manner. MPT53 induces disulfide bond formation at C210 on TAK1 to facilitate its interaction with TRAFs and TAB1, thus activating TAK1 to induce the expression of pro-inflammatory cytokines. Furthermore, MPT53 and its disulfide oxidoreductase activity is required for Mtb to induce the host inflammatory responses via TAK1. Our findings provide an alternative pathway for host signalling proteins to sense Mtb infection and may favour the improvement of current vaccination strategies.Entities:
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Year: 2019 PMID： 31110366 DOI： 10.1038/s41564-019-0436-3
Source DB: PubMed Journal: Nat Microbiol ISSN： 2058-5276 Impact factor: 17.745