Salmonella Coiled-Coil- and TIR-Containing TcpS Evades the Innate Immune System and Subdues Inflammation

Publication date: 16 July 2019Source: Cell Reports, Volume 28, Issue 3Author(s): Dan Xiong, Li Song, Shizhong Geng, Yang Jiao, Xiaohui Zhou, Hongqin Song, Xilong Kang, Yi Zhou, Xiulong Xu, Jun Sun, Zhiming Pan, Xinan JiaoSummaryToll-like receptors (TLRs) activate innate immunity via interactions between their Toll/interleukin-1 (IL-1) receptor (TIR) domain and downstream adaptor proteins. Here we report that Salmonella Enteritidis produces a secreted protein (TcpS) that contains both a TIR domain and a coiled-coil domain. TcpS blocks MyD88- and TRIF-mediated TLR signaling, inhibits inflammatory responses, and promotes bacterial survival. Early-stage immune evasion by TcpS results in severe tissue damage in the late stage of infection and contributes to Salmonella virulence. TcpS-derived peptides inhibit nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) activation and reduce lipopolysaccharide (LPS)-elicited systemic inflammation. Therapeutic peptide administration alleviates weight loss of mice infected with H1N1 influenza. Importantly, maximal TcpS-mediated TLR inhibition requires the critical TIR-TcpS residues Y191 and I284, as well as TcpS homodimerization via its N-terminal coiled-coil domain. Our study unveils a mechanism in which TcpS suppresses innate immunity via both its homodimerization and interaction with MyD88. TcpS is also a potential therapeutic agent for inflammation-associated diseases.Graphical Abstract

Source: Cell Reports - July 17, 2019 Category: Cytology Source Type: research