Abstract
Enteropathogenic Escherichia coli (EPEC) cells adhere to gut epithelial cells through intimin alpha: the ligand for a bacterially derived epithelial transmembrane protein called the translocated intimin receptor. Citrobacter rodentium colonizes the mouse colon in a similar fashion and uses a different intimin: intimin beta. Intimin alpha was found to costimulate submitogenic signals through the T cell receptor. Dead intimin beta+ C. rodentium, intimin alpha-transfected C. rodentium or E. coli strain K12, and EPEC induced mucosal hyperplasia identical to that caused by C. rodentium live infection, as well as a massive T helper cell-type 1 immune response in the colonic mucosa. Mutation of cysteine-937 of intimin to alanine reduced costimulatory activity in vitro and prevented immunopathology in vivo. The mucosal changes elicited by C. rodentium were interferon-gamma-dependent. Immunopathology induced by intimin enables the bacteria to promote conditions that are favorable for increased microbial colonization.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adhesins, Bacterial*
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Animals
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Bacterial Adhesion
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Bacterial Outer Membrane Proteins / pharmacology
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Bacterial Outer Membrane Proteins / physiology*
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Carrier Proteins*
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Citrobacter / pathogenicity*
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Colitis / immunology
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Colitis / microbiology*
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Colitis / pathology
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Colon / immunology
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Colon / microbiology
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Colon / pathology*
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Cytokines / biosynthesis
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Cytokines / genetics
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Enterobacteriaceae Infections / immunology
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Enterobacteriaceae Infections / microbiology*
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Enterobacteriaceae Infections / pathology
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Escherichia coli / pathogenicity
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Escherichia coli Proteins*
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Hyperplasia
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Interferon-gamma / physiology
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Intestinal Mucosa / immunology
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Intestinal Mucosa / microbiology
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Intestinal Mucosa / pathology
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Ligands
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Lymphocyte Activation
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Mice
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Mice, Inbred BALB C
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Receptors, Cell Surface / metabolism
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T-Lymphocytes / immunology
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Th1 Cells / immunology*
Substances
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Adhesins, Bacterial
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Bacterial Outer Membrane Proteins
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Carrier Proteins
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Cytokines
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Escherichia coli Proteins
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Ligands
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Receptors, Cell Surface
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Tir protein, E coli
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eaeA protein, E coli
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Interferon-gamma