4 Despite much attention on the role of specific adaptive immunity in the maintenance of immune homeostasis in the intestinal mucosa in this model system, 5 little is known about the contribution of the innate immune response. In common with many murine models of intestinal inflammation, the adoptive transfer of CD4 +CD45RB hi T cells into syngeneic SCID or RAG −/− recipients results in the development of chronic colitis in conventionally housed animals but not in a germ free environment. Recently, Rakoff-Nahoum et al have shown that constitutive activation of TLRs plays an important role in epithelial homeostasis and cytoprotection in the intestine.

PAMPs can bind to “Toll-like receptors” (TLRs) thereby eliciting an innate immune response. This cell type is exposed to a complex bacterial laden environment containing a vast number of toxic and proinflammatory substances that can be referred to as pathogen associated molecular patterns (PAMPs). The colonic epithelium represents the interface between the mucosal surface and the contents of the intestinal lumen and may be considered a component of the innate immune system. 1 In addition, identification of NOD2 gene mutations as a genetic factor that enhances susceptibility to the development of Crohn’s disease provides a direct link between genetic predisposition, commensal bacteria, and the innate immune system in the pathogenesis of IBD. For example, the bacterial protein flagellin has been recently identified as a dominant antigen in several murine models of intestinal inflammation as well as in patients with Crohn’s disease. Interest has recently focused on the role of the innate immune system in maintaining homeostasis of the mucosal immune system in the presence of gut flora. Growing evidence from clinical observations of patients with inflammatory bowel disease (IBD) as well as studies of animal models of intestinal inflammation suggests that the pathogenesis of IBD involves a dysregulated immune response to the commensal bacterial flora in the intestinal tract of genetically susceptible individuals. PAMPs, pathogen associated molecular patterns.RT-PCR, reverse transcription-polymerase chain reaction.These innate immune responses may play a role in the pathogenesis of colitis in SCID adoptive transfer models in mice and possibly in patients with IBD. In vivo IFN-γ immunoneutralisation studies failed to demonstrate any alteration in RegIIIβ or γ expression.Ĭonclusions: Thus bacterial colonisation of the colon independently activates two distinct innate immune cell types at the mucosal interface with the colonic lumen, intestinal epithelial cells, and IENK cells, a response that may be regulated by the adaptive immune system. The cellular source for IFN-γ on monoassociation of SCID mice with Schaedler’s E coli was localised to a subset of intraepithelial natural killer (IENK) cells that express asialo-GM1. Induction of these genes was reproduced by chronic monoassociation of germ free SCID mice with either of two separate gut commensal bacterial species- segmented filamentous bacteria and Schaedler’s Escherichia coli. Results: Using quantitative reverse transcription-polymerase chain reaction, we showed that RegIIIβ, RegIIIγ, and IFN-γ were constitutively expressed in the colon of conventionally housed SCID mice compared with either germ free SCID or conventionally housed BALB/c mice. The two most consistently induced gene groups were RegIIIβ and γ as well as interferon γ (IFN-γ) response genes. Methods: Using gene expression profiling of colonic RNA from C.B17.SCID germ free mice and those colonised with altered Schaedler’s flora, we investigated the innate immune response to bacterial colonisation in vivo. Background and aims: The mechanisms by which commensal bacteria provoke intestinal inflammation in animal models of inflammatory bowel disease (IBD) remain incompletely defined, leading to increasing interest in the innate immune response of the colonic mucosa to bacterial colonisation.

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