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

¹ Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
² Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, and Department of Biology, University of Pennsylvania, Philadelphia, PA, USA
³ Department of Biology, University of Pennsylvania, Philadelphia, PA, USA, and Department of Microbiology, Immunology and Virology, Medical Faculty, Uzhhorod National University 1, Uzhhorod, Ukraine
⁴ Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA
⁵ Department of Biology, University of Pennsylvania, Philadelphia, PA, USA

Correspondence to:
Correspondence to:
Dr G D Wu
600 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104-6144, USA; gdwu{at}mail.med.upenn.edu

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 RegIIIß and as well as interferon (IFN-) response genes.

Results: Using quantitative reverse transcription-polymerase chain reaction, we showed that RegIIIß, RegIII, and IFN- were constitutively expressed in the colon of 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 Schaedler’s Escherichia coli. The cellular source for IFN- 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- immunoneutralisation studies failed to demonstrate any alteration in RegIIIß or 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 SCID adoptive transfer models in mice and possibly in patients with IBD.

Abbreviations: IBD, inflammatory bowel disease; IFN-, interferon ; ASF, altered Schaedler’s flora; SFB, segmented filamentous bacteria; RT-PCR, reverse transcription-polymerase chain reaction; PAMPs, pathogen associated molecular patterns; TLR, Toll-like receptor; NK, natural killer; IENK, intraepithelial natural killer; CFU, colony forming units; Upase, uridine phosphorylase; PAP, pancreatitis associated protein

Keywords: interferon ; colon; SCID mice; bacteria; innate immunity

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