Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota

Abstract

There are now many experimental models of inflammatory bowel disease (IBD), most of which are due to induced mutations in mice that result in an impaired homeostasis with the intestinal microbiota. These models can be clustered into several broad categories that, in turn, define the crucial cellular and molecular mechanisms of host microbial interactions in the intestine. The first of these components is innate immunity defined broadly to include both myeloid and epithelial cell mechanisms. A second component is the effector response of the adaptive immune system, which, in most instances, comprises the CD4+ T cell and its relevant cytokines. The third component is regulation, which can involve multiple cell types, but again particularly involves CD4+ T cells. Severe impairment of a single component can result in disease, but many models demonstrate milder defects in more than one component. The same is true for both spontaneous models of IBD, C3H/HeJBir and SAMPI/Yit mice. The thesis is advanced that 'multiple hits' or defects in these interacting components is required for IBD to occur in both mouse and human.

Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach

“…This fact is supported by the therapeutic benefits of antibiotic and probiotic treatment in IBD patients, 40,41 the observation that specific enteric flora are found more commonly in patients than in controls, 42,43 and studies in a variety of murine strains in which 'spontaneous' colitis seems to be entirely dependent on the presence of a luminal flora. [44][45][46] Autophagy has an important role in physiological and pathological processes, such as degradation of cytoplasmic components, cellular response to nutrient starvation and apoptosis. 47,48 Moreover, autophagy is also relevant in innate 49,50 and adaptive immunity.…”

Enterotoxigenic Bacteroides fragilis: A potential instigator of colitis

“…These mice are inbred but lack defined defects in host immunity as are usually present in other current murine models of IBD focused on examining the role of the colonic flora in disease. 22,23 Identification of colitis in C57BL/6 mice colonized with ETBF suggest that these organisms are potent proinflammatory bacteria. IBD is thought to result from a dysregulated mucosal immune response to the colonic flora in genetically susceptible individuals.…”

STAT3 in immune responses and inflammatory bowel diseases

“…A number of animal models dealing with IBDs have been previously established (recently reviewed in [65]). As mentioned above, mutations in the gene encoding NOD2 result in susceptibility to Crohn's disease, particularly small intestinal disease [38,39].…”