Enterohemorrhagic Escherichia coli Tir inhibits TAK1 activation and mediates immune evasion.

Autor: Zhou R; a Department 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 China., Chen Z; a Department 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 China., Hao D; a Department 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 China., Wang Y; b Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy , Army Medical University , Chongqing , People's Republic of China., Zhang Y; a Department 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 China., Yi X; c School of Biomedical Engineering , Tianjin Medical University , Tianjin , People's Republic of China., Lyu LD; a Department 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 China., Liu H; d Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital , Tongji University School of Medicine , Shanghai , People's Republic of China., Zou Q; b Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy , Army Medical University , Chongqing , People's Republic of China., Chu Y; a Department 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 China., Ge B; d Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital , Tongji University School of Medicine , Shanghai , People's Republic of China.; e Department of Microbiology and Immunology , Tongji University School of Medicine , Shanghai , People's Republic of China., Yan D; a Department 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 China.
Jazyk: angličtina
Zdroj: Emerging microbes & infections [Emerg Microbes Infect] 2019; Vol. 8 (1), pp. 734-748.
DOI: 10.1080/22221751.2019.1620589
Abstrakt: 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.
Databáze: MEDLINE