Role of bacterial intimin in colonic hyperplasia and inflammation.
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.
Department of Paediatric Gastroenterology, St. Bartholomews and the Royal London School of Medicine and Dentistry, London EC1A 7BE, UK.
L M
LM
Higgins
G
G
Frankel
I
I
Connerton
N S
NS
Gonçalves
G
G
Dougan
T T
TT
MacDonald
D018829:Adhesins, Bacterial; D000818:Animals; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology / Q000502:physiology*; D002352:Carrier Proteins; D002954:Citrobacter / Q000472:pathogenicity*; D003092:Colitis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004756:Enterobacteriaceae Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D004926:Escherichia coli / Q000472:pathogenicity; D029968:Escherichia coli Proteins; D006965:Hyperplasia; D007371:Interferon-gamma / Q000502:physiology; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011956:Receptors, Cell Surface / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D016207:Cytokines; D029968:Escherichia coli Proteins; D008024:Ligands; D011956:Receptors, Cell Surface; C109287:Tir protein, E coli; C073819:eaeA protein, E coli; D007371:Interferon-gamma