Enterohemorrhagic Escherichia coli Tir inhibits TAK1 activation and mediates immune evasion
Many pathogens infect hosts through various immune evasion strategies. However, the molecular mechanisms by which pathogen proteins modulate and evade the host immune response remain unclear. Enterohemorrhagic Escherichia coli (EHEC) is a pathological strain that can induce mitogen-activated protein...
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Taylor & Francis Group
2019-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2019.1620589 |
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| author | Ruixue Zhou Zijuan Chen Doudou Hao Yu Wang Yihua Zhang Xianfu Yi Liang-Dong Lyu Haipeng Liu Quanming Zou Yiwei Chu Baoxue Ge Dapeng Yan |
| author_facet | Ruixue Zhou Zijuan Chen Doudou Hao Yu Wang Yihua Zhang Xianfu Yi Liang-Dong Lyu Haipeng Liu Quanming Zou Yiwei Chu Baoxue Ge Dapeng Yan |
| author_sort | Ruixue Zhou |
| collection | DOAJ |
| description | Many pathogens infect hosts through various immune evasion strategies. However, the molecular mechanisms by which pathogen proteins modulate and evade the host immune response remain unclear. Enterohemorrhagic Escherichia coli (EHEC) is a pathological strain that can induce mitogen-activated protein (MAP) kinase (Erk, Jnk and p38 MAPK) and NF-κB pathway activation and proinflammatory cytokine production, which then causes diarrheal diseases such as hemorrhagic colitis and hemolytic uremic syndrome. Transforming growth factor β-activated kinase-1 (TAK1) is a key regulator involved in distinct innate immune signalling pathways. Here we report that EHEC translocated intimin receptor (Tir) protein inhibits the expression of EHEC-induced proinflammatory cytokines by interacting with the host tyrosine phosphatase SHP-1, which is dependent on the phosphorylation of immunoreceptor tyrosine-based inhibition motifs (ITIMs). Mechanistically, the association of EHEC Tir with SHP-1 facilitated the recruitment of SHP-1 to TAK1 and inhibited TAK1 phosphorylation, which then negatively regulated K63-linked polyubiquitination of TAK1 and downstream signal transduction. Taken together, these results suggest that EHEC Tir negatively regulates proinflammatory responses by inhibiting the activation of TAK1, which is essential for immune evasion and could be a potential target for the treatment of bacterial infection. |
| format | Article |
| id | doaj-art-9ae96192bf31483494a8b7ee9a4bdb45 |
| institution | DOAJ |
| issn | 2222-1751 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-9ae96192bf31483494a8b7ee9a4bdb452025-08-20T03:17:32ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512019-01-018173474810.1080/22221751.2019.1620589Enterohemorrhagic Escherichia coli Tir inhibits TAK1 activation and mediates immune evasionRuixue Zhou0Zijuan Chen1Doudou Hao2Yu Wang3Yihua Zhang4Xianfu Yi5Liang-Dong Lyu6Haipeng Liu7Quanming Zou8Yiwei Chu9Baoxue Ge10Dapeng Yan11Department of Immunology, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, People’s Republic of ChinaDepartment of Immunology, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, People’s Republic of ChinaDepartment of Immunology, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, People’s Republic of ChinaDepartment of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Army Medical University, Chongqing, People’s Republic of ChinaDepartment of Immunology, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, People’s Republic of ChinaSchool of Biomedical Engineering, Tianjin Medical University, Tianjin, People’s Republic of ChinaDepartment of Immunology, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, People’s Republic of ChinaShanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaDepartment of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Army Medical University, Chongqing, People’s Republic of ChinaDepartment of Immunology, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, People’s Republic of ChinaShanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaDepartment of Immunology, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, People’s Republic of ChinaMany pathogens infect hosts through various immune evasion strategies. However, the molecular mechanisms by which pathogen proteins modulate and evade the host immune response remain unclear. Enterohemorrhagic Escherichia coli (EHEC) is a pathological strain that can induce mitogen-activated protein (MAP) kinase (Erk, Jnk and p38 MAPK) and NF-κB pathway activation and proinflammatory cytokine production, which then causes diarrheal diseases such as hemorrhagic colitis and hemolytic uremic syndrome. Transforming growth factor β-activated kinase-1 (TAK1) is a key regulator involved in distinct innate immune signalling pathways. Here we report that EHEC translocated intimin receptor (Tir) protein inhibits the expression of EHEC-induced proinflammatory cytokines by interacting with the host tyrosine phosphatase SHP-1, which is dependent on the phosphorylation of immunoreceptor tyrosine-based inhibition motifs (ITIMs). Mechanistically, the association of EHEC Tir with SHP-1 facilitated the recruitment of SHP-1 to TAK1 and inhibited TAK1 phosphorylation, which then negatively regulated K63-linked polyubiquitination of TAK1 and downstream signal transduction. Taken together, these results suggest that EHEC Tir negatively regulates proinflammatory responses by inhibiting the activation of TAK1, which is essential for immune evasion and could be a potential target for the treatment of bacterial infection.https://www.tandfonline.com/doi/10.1080/22221751.2019.1620589EHECTirITIMSHP-1TAK1immune evasion |
| spellingShingle | Ruixue Zhou Zijuan Chen Doudou Hao Yu Wang Yihua Zhang Xianfu Yi Liang-Dong Lyu Haipeng Liu Quanming Zou Yiwei Chu Baoxue Ge Dapeng Yan Enterohemorrhagic Escherichia coli Tir inhibits TAK1 activation and mediates immune evasion Emerging Microbes and Infections EHEC Tir ITIM SHP-1 TAK1 immune evasion |
| title | Enterohemorrhagic Escherichia coli Tir inhibits TAK1 activation and mediates immune evasion |
| title_full | Enterohemorrhagic Escherichia coli Tir inhibits TAK1 activation and mediates immune evasion |
| title_fullStr | Enterohemorrhagic Escherichia coli Tir inhibits TAK1 activation and mediates immune evasion |
| title_full_unstemmed | Enterohemorrhagic Escherichia coli Tir inhibits TAK1 activation and mediates immune evasion |
| title_short | Enterohemorrhagic Escherichia coli Tir inhibits TAK1 activation and mediates immune evasion |
| title_sort | enterohemorrhagic escherichia coli tir inhibits tak1 activation and mediates immune evasion |
| topic | EHEC Tir ITIM SHP-1 TAK1 immune evasion |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2019.1620589 |
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