Role of bacteria in the etiopathogenesis of inflammatory bowel disease.
Increased numbers of mucosa-associated Escherichia coli are observed in both of the major inflammatory bowel diseases, Crohn d' disease (CD) and ulcerative colitis (UC). A potential pathophysiological link between the presence of pathogenic invasive bacteria and genetic host susceptibility of patients with ileal CD is suspected. In CD patients, with increased ileal expression of the CEACAM6 molecule acting as a receptor recognized by type 1 pilus bacterial adhesin, and with the identification of mutations in the NOD2-encoding gene, the presence of pathogenic invasive bacteria could be the link between abnormal ileal bacterial colonization and innate immune responses to invasive bacteria. In a susceptible host, the sequential etiological steps of the disease induced by adherent-invasive E. coli (AIEC) are: (1) abnormal colonization via binding to the CEACAM6 receptor, which is overexpressed in the ileal mucosa of CD patients; (2) ability to adhere to and to invade intestinal epithelial cells, which allows bacteria to cross the mucosal barrier; (3) survival and replication within infected macrophages in the lamina propria; and (4) induction of tumor necrosis factor-alpha secretion and granuloma formation.
Barnich
Nicolas
N
Pathogenie Bacterienne Intestinale, USC INRA 2018, Universite d'Auvergne, Centre Biomedical de Recherche et Valorisation, 28 Place Henri Dunant, Clermont-Ferrand 63000, France. nicolas.barnich@u-clermont1.fr
Darfeuille-Michaud
Arlette
A
D015703:Antigens, CD / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004927:Escherichia coli Infections / Q000150:complications*; D058851:GPI-Linked Proteins; D006099:Granuloma / Q000209:etiology; D006801:Humans; D007082:Ileum / Q000382:microbiology; D015212:Inflammatory Bowel Diseases / Q000209:etiology*; D008264:Macrophages / Q000382:microbiology; D053473:Nod2 Signaling Adaptor Protein / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000502:physiology
D015703:Antigens, CD; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D053473:Nod2 Signaling Adaptor Protein; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2