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.
Higgins
L M
LM
Department of Paediatric Gastroenterology, St. Bartholomews and the Royal London School of Medicine and Dentistry, London EC1A 7BE, UK.
Frankel
G
G
Connerton
I
I
Gonçalves
N S
NS
Dougan
G
G
MacDonald
T T
TT
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