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

Cell Signal. 2013 Sep;25(9):1887-94. doi: 10.1016/j.cellsig.2013.05.020. Epub 2013 May 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cytokines / immunology
  • Enteropathogenic Escherichia coli / physiology*
  • Escherichia coli Infections / immunology*
  • Escherichia coli Infections / metabolism
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / immunology*
  • Escherichia coli Proteins / metabolism
  • Host-Parasite Interactions*
  • Humans
  • Immunoreceptor Tyrosine-Based Activation Motif*
  • 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
  • TNF Receptor-Associated Factor 6 / metabolism
  • Ubiquitination


  • Cytokines
  • Escherichia coli Proteins
  • Receptors, Cell Surface
  • TNF Receptor-Associated Factor 6
  • Tir protein, E coli
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11