Abnormalities in the handling of intracellular bacteria in Crohn's disease: a link between infectious etiology and host genetic susceptibility.
The etiology of Crohn's disease (CD) is still poorly understood, but recent advances have highlighted the importance of the innate immune system and the critical relationship between the gut flora and the intestinal mucosa. Several combinations of genetic factors predisposing to CD have been described, with the most significant replicable associations including genes for intracellular receptors of bacterial cell walls (NOD2/CARD15) and for bacterial clearance and antigen processing via autophagy (ATG16L1 and IRGM). One theoretical link between susceptibility genes NOD2/CARD15, ATG16L1, and IRGM is that CD is primarily induced by the presence of a dysfunctional immunological response to persistent infection by intracellular bacterial pathogens such as Mycobacterium avium subspecies paratuberculosis or adherent-invasive Escherichia coli, both first-rank candidates on the basis of host genetic susceptibility, which concerns impaired functions in the defense against intracellular bacteria.
Glasser
Anne-Lise
AL
Pathogénie Bactérienne Intestinale, Université d'Auvergne, JE 2526, USC INRA 2018, Clermont-Ferrand, France.
Darfeuille-Michaud
Arlette
A
D015703:Antigens, CD / Q000378:metabolism; D001343:Autophagy; D001419:Bacteria / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification; D001424:Bacterial Infections / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D058851:GPI-Linked Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D007422:Intestines / Q000382:microbiology; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism
D015703:Antigens, CD; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D016207:Cytokines; D058851:GPI-Linked Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D011494:Protein Kinases