Salmonella Coiled-Coil- and TIR-Containing TcpS Evades the Innate Immune System and Subdues Inflammation
Summary: Toll-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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-07-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719308216 |
| _version_ | 1817987963619901440 |
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| author | Dan Xiong Li Song Shizhong Geng Yang Jiao Xiaohui Zhou Hongqin Song Xilong Kang Yi Zhou Xiulong Xu Jun Sun Zhiming Pan Xinan Jiao |
| author_facet | Dan Xiong Li Song Shizhong Geng Yang Jiao Xiaohui Zhou Hongqin Song Xilong Kang Yi Zhou Xiulong Xu Jun Sun Zhiming Pan Xinan Jiao |
| author_sort | Dan Xiong |
| collection | DOAJ |
| description | Summary: Toll-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. : Xiong et al. show that Salmonella subverts host TLR signaling by delivering a protein containing a TIR domain and a coiled-coil domain, TcpS. Immune evasion by TcpS supports early bacterial infection, which enables late-stage virulence and inflammation storm. TcpS-derived peptides reduce LPS-elicited systemic inflammation and are protective against influenza challenge in mice. Keywords: Salmonella, coiled-coil, TIR, TcpS, TLR signaling, immune evasion, inflammation, therapeutic peptide |
| first_indexed | 2024-04-14T00:28:54Z |
| format | Article |
| id | doaj.art-09c9361d2ae34eff8b883d25774b990c |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-14T00:28:54Z |
| publishDate | 2019-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-09c9361d2ae34eff8b883d25774b990c2022-12-22T02:22:37ZengElsevierCell Reports2211-12472019-07-01283804818.e7Salmonella Coiled-Coil- and TIR-Containing TcpS Evades the Innate Immune System and Subdues InflammationDan Xiong0Li Song1Shizhong Geng2Yang Jiao3Xiaohui Zhou4Hongqin Song5Xilong Kang6Yi Zhou7Xiulong Xu8Jun Sun9Zhiming Pan10Xinan Jiao11Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu 225009, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu 225009, ChinaJiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu 225009, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu 225009, ChinaJiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu 225009, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu 225009, ChinaJiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu 225009, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu 225009, ChinaDepartment of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT 06269, USAJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, ChinaJiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu 225009, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu 225009, ChinaJiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu 225009, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu 225009, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, ChinaDepartment of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USAJiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu 225009, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu 225009, China; Corresponding authorJiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou University, Yangzhou, Jiangsu 225009, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu 225009, China; Corresponding authorSummary: Toll-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. : Xiong et al. show that Salmonella subverts host TLR signaling by delivering a protein containing a TIR domain and a coiled-coil domain, TcpS. Immune evasion by TcpS supports early bacterial infection, which enables late-stage virulence and inflammation storm. TcpS-derived peptides reduce LPS-elicited systemic inflammation and are protective against influenza challenge in mice. Keywords: Salmonella, coiled-coil, TIR, TcpS, TLR signaling, immune evasion, inflammation, therapeutic peptidehttp://www.sciencedirect.com/science/article/pii/S2211124719308216 |
| spellingShingle | Dan Xiong Li Song Shizhong Geng Yang Jiao Xiaohui Zhou Hongqin Song Xilong Kang Yi Zhou Xiulong Xu Jun Sun Zhiming Pan Xinan Jiao Salmonella Coiled-Coil- and TIR-Containing TcpS Evades the Innate Immune System and Subdues Inflammation Cell Reports |
| title | Salmonella Coiled-Coil- and TIR-Containing TcpS Evades the Innate Immune System and Subdues Inflammation |
| title_full | Salmonella Coiled-Coil- and TIR-Containing TcpS Evades the Innate Immune System and Subdues Inflammation |
| title_fullStr | Salmonella Coiled-Coil- and TIR-Containing TcpS Evades the Innate Immune System and Subdues Inflammation |
| title_full_unstemmed | Salmonella Coiled-Coil- and TIR-Containing TcpS Evades the Innate Immune System and Subdues Inflammation |
| title_short | Salmonella Coiled-Coil- and TIR-Containing TcpS Evades the Innate Immune System and Subdues Inflammation |
| title_sort | salmonella coiled coil and tir containing tcps evades the innate immune system and subdues inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719308216 |
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