Abstract
BackgroundThe colonic mucus layer plays a critical role in intestinal homeostasis by limiting contact between luminal bacteria and the mucosal immune system. A defective mucus barrier in animal models allows bacterial contact with the intestinal epithelium and results in spontaneous colitis. A defective mucus barrier is also a key feature of active ulcerative colitis (UC). Alterations in the immune compartment due to intestinal bacterial breach in mice lacking the colon mucus barrier have not been characterized and correlated to active UC.AimsTo characterize alterations in the immune compartment due to intestinal bacterial breach in Muc2−/− mice, which lack the colon mucus barrier, and correlate the findings to active UC.MethodsBacterial contact with colon epithelium and penetration into colon tissue was examined in Muc2−/− mice and colon biopsies from patients with active UC using fluorescence microscopy and qPCR. Neutrophils, lymphocytes, CD103+ dendritic cell subsets and macrophages in colon from Muc2−/− mice and biopsies from UC patients were quantitated by flow cytometry.ResultsInflamed UC patients and Muc2−/− mice had bacteria in contact with the colon epithelium. Bacterial rRNA was present in colonic mucosa in humans and Muc2−/− mice and in the draining lymph nodes of mice. Inflamed Muc2−/− mice and UC patients had elevated colon neutrophils, T cells and macrophages while a reduced frequency of CD103+ DCs was present in the inflamed colon of both mice and humans.ConclusionsThe parallel features of the colon immune cell compartment in Muc2−/− mice and UC patients supports the usefulness of this model to understand the early phase of spontaneous colitis and will provide insight into novel strategies to treat UC.
Highlights
The colon lumen contains a massive amount of commensal bacteria that make essential contributions to metabolism and homeostasis, but aberrant reactivity to commensals can result in inflammatory bowel disease in genetically susceptible individuals
Inflamed Muc22/2 mice and ulcerative colitis (UC) patients had elevated colon neutrophils, T cells and macrophages while a reduced frequency of CD103+ dendritic cell (DC) was present in the inflamed colon of both mice and humans
The parallel features of the colon immune cell compartment in Muc22/2 mice and UC patients supports the usefulness of this model to understand the early phase of spontaneous colitis and will provide insight into novel strategies to treat UC
Summary
The colon lumen contains a massive amount of commensal bacteria that make essential contributions to metabolism and homeostasis, but aberrant reactivity to commensals can result in inflammatory bowel disease in genetically susceptible individuals. The colonic barrier plays an important role to ensure that there is normally minimal contact between luminal bacteria and the mucosal immune system [1,2]. Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease characterized by mucosal inflammation restricted to the colon that is accompanied by recurrent periods of bloody, loose stools [5]. It almost invariably affects the rectum and may involve the sigmoid colon or the entire colon. The colonic mucus layer plays a critical role in intestinal homeostasis by limiting contact between luminal bacteria and the mucosal immune system.
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