bilis (ATCC 51630). The authors showed that a rapid and persistent immunoglobulin G immune response to the organisms of the flora predated the development of colitis in infected mice and this was matched by a cytokine profile similar to
that seen in human IBD with elevated interferon γ (IFNγ), tumour necrosis factor α (TNFα), IL-6 and IL-12, but modest secretion of IL-10. The study suggested that perhaps the Helicobacter organisms are responsible for orchestrating an immune reaction, or loss of tolerance, to harmless members of the resident microbiota. A recent study by Matharu et al. (2009) has demonstrated the importance of a functioning Toll-like receptor 4 (TLR4) receptor in H. hepaticus-induced colitis. This study utilized GSK-3 beta pathway mice with TLR4-/-, IL-10-/- or both TLR4-/-and IL-10-/- and H. hepaticus (ATCC 51449). The dual-immunodeficient TLR4-/-× IL-10-/- mice demonstrated both an earlier onset and higher incidence of colitis than IL-10-/- mice. In addition, a dysregulated immune response
was seen after infection in the TLR4-/-× IL-10-/- mice with resultant IFN-γ/IL-17-secreting Foxp3+ Treg cell accumulation in the colonic lamina propria and a subsequent failure to control disease. This observation compliments the finding that genetic polymorphisms in MAST3, a TLR4 signal modulator confer an increased risk of human IBD (Labbéet al., 2008). Finally, Chow & Mazmanian (2010) have recently published a landmark paper examining the importance Ixazomib mw of the type VI secretion system (T6SS) to H. hepaticus (ATCC 51449) in terms of its activity being either symbiotic or pathogenic to the host organism. This study eloquently showed that wild-type T6SS organisms appear to promote an anti-inflammatory environment within intestinal epithelial cells (IECs) while mutant T6SS organisms show increased colonization of the murine intestine, increased intracellular colonization within IECs and, most importantly, a broad and apparently TH17-based host immune response to the presence of the organism. The study utilized various mouse models and a mouse IEC line. The importance of this study Etofibrate is that intraspecies
bacterial heterogeneity has been demonstrated to be as important as host heterogeneity in defining the ultimate host phenotype in an IBD model. The human story of Helicobacter infection with relation to IBD probably begins with the findings of Fennell et al. (1984) and Totten et al. (1985) from Seattle in the 1980s who isolated perhaps for the first, and only time since, novel Helicobacter organisms from colitic (and not simply diarrhoeal) humans. The humans in question were homosexual men with proctitis and the Helicobacter in question were isolated from rectal swabs, and classified at the time within the genus Campylobacter, labelled broadly as Campylobacter-like organisms (CLO). These CLO organisms were isolated from 33 of 201 (16.4%) symptomatic men and 14 of 155 (9.