Bacterial factors in inflammatory bowel disease pathogenesis

Abstract

Intestinal bacteria and their products appear to contribute significantly to the pathogenesis of inflammatory bowel disease (IBD). Both commensal bacterial products, including lipopolysaccharides (LPS) and lipoteichoic acids, and potential pathogens may be implicated. Lamina propria cells in the intestinal mucosa are exposed to luminal LPS especially in the colon and distal ileum. CD14, the receptor for LPS—LPS binding protein complex, is expressed on blood monocytes recently recruited to the IBD mucosa. Activation of CD14 positive mononuclear phagocytes occurs at pg/ml concentrations of LPS resulting in protean biological effects, including secretion of proinflammatory cytokines, especially TNF-a, chemokines, proteases, and reactive oxygen and nitrogen species. Neutrophils recruited to the lesion of acute colitis induced in mice by oral dextran sulphate sodium similarly express CD14. The phenotype of inflammatory cells in the lesions of IBD therefore suggests a mechanism for persisting mucosal inflammation.

Recent insights into the importance of innate immunity as a front-line, early-detection antimicrobial defence system may be relevant to IBD pathogenesis. Innate immunity detects unique bacterial carbohydrate or lipid molecules using cell surface receptors, especially those on macrophages. Activation of these receptors initiates a discrete IL-12, interferon gamma pathway essential to macrophage killing of mycobacteria and some enteric bacterial pathogens. Inherited deficiency of peptides or their receptors in the IL-12—interferon gamma pathway results in susceptibility to mycobacterial and Salmonella infections as well as affecting granuloma formation in tissue. These recent findings suggest new avenues for exploring possible susceptibility factors in IBD.