Enteropathogenic Escherichia coli Tir recruits cellular SHP-2 through ITIM motifs to suppress host immune response

• Published in: Cellular signalling 2013-09, Vol.25 (9), p.1887-1894
• Main Authors: Yan, Dapeng, Quan, Heming, Wang, Lin, Liu, Feng, Liu, Haipeng, Chen, Jianxia, Cao, Xuetao, Ge, Baoxue
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Cytokines - immunology; Enteropathogenic Escherichia coli; Enteropathogenic Escherichia coli - physiology; Escherichia coli; Escherichia coli Infections - immunology; Escherichia coli Infections - metabolism; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - immunology; Escherichia coli Proteins - metabolism; Host-Parasite Interactions; Humans; Immune response; Immunoreceptor Tyrosine-Based Activation Motif; ITIM; Mice; Mice, Inbred C57BL; Phosphorylation; Protein Binding; Protein Interaction Maps; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - immunology; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - metabolism; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - immunology; Receptors, Cell Surface - metabolism; SHP-2; Tir; TNF Receptor-Associated Factor 6 - metabolism; TRAF6; Ubiquitination
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2013.05.020

Immune responses to pathogens are regulated by immune receptors containing either an immunoreceptor tyrosine-based activation motif (ITAM) or an immunoreceptor tyrosine-based inhibitory motif (ITIM). The important diarrheal pathogen enteropathogenic Escherichia coli (EPEC) require delivery and insertion of the bacterial translocated intimin receptor (Tir) into the host plasma membrane for pedestal formation. The C-terminal region of Tir, encompassing Y483 and Y511, shares sequence similarity with cellular ITIMs. Here, we show that EPEC Tir suppresses the production of inflammatory cytokines by recruitment of SHP-2 and subsequent deubiquitination of TRAF6 in an ITIM dependent manner. Our findings revealed a novel mechanism by which the EPEC utilize its ITIM motifs to suppress and evade the host innate immune response, which could lead to the development of novel therapeutics to prevent bacterial infection. •Our previous work have shown Tir interacts with tyrosine phosphatase SHP-1.•Here, we reported Tir suppresses the production of cytokines through SHP-2.•Our findings revealed a new mechanism of bacteria evasion from host cells.