TITLE

Activation of ReqIIIβ/γ small gamma and interferon γ small gamma expression in the intestinal tract of SCID mice: an innate response to bacterial colonisation of the gut

AUTHOR(S)
Keilbaugh, S A; Shin, M E; Banchereau, R F; Mcvay, L D; Boyko, N; Artis, D; Cebra, J J; Wu, G D
PUB. DATE
May 2005
SOURCE
Gut;May2005, Vol. 54 Issue 5, p623
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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. 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. The two most consistently induced gene groups were RegIllβ and γ as well as interferon γ (IFN-γ) response genes. Results: Using quantitative reverse transcription-polymerase chain reaction, we showed that RegIIIβ, Regillγ, and IFN-γ were constitutively expressed in the colon 0f conventionally housed SCID mice compared with either germ free SCID or conventionally housed BALB/c mice. 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 Schoedler's Escherichia coli. 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. In vivo IFN-γ immunoneutralisation studies failed to demonstrate any alteration in Reglllβ or γ expression. Conclusions: 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. These innate immune responses may play a role in the pathogenesis of colitis in SOD adoptive transfer models in mice and possibly in patients with IBD.
ACCESSION #
16886333

 

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