title: Enteropathogenic Escherichia coli Tir recruits cellular SHP-2 through ITIM motifs to suppress host immune response.
abstract: 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.
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Yan
authors.forename: Heming
authors.initials: H
authors.lastname: Quan
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Haipeng
authors.initials: H
authors.lastname: Liu
authors.forename: Jianxia
authors.initials: J
authors.lastname: Chen
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
authors.forename: Baoxue
authors.initials: B
authors.lastname: Ge
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D054308:Enteropathogenic Escherichia coli / Q000502:physiology*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006790:Host-Parasite Interactions; D006801:Humans; D061625:Immunoreceptor Tyrosine-Based Activation Motif; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011485:Protein Binding; D060066:Protein Interaction Maps; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000276:immunology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D016207:Cytokines; D029968:Escherichia coli Proteins; D011956:Receptors, Cell Surface; D048029:TNF Receptor-Associated Factor 6; C109287:Tir protein, E coli; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11