Immunization with cytolethal distending toxin B produces autoantibodies to vinculin and small bowel bacterial changes in a rat model of postinfectious irritable bowel syndrome

초록

Background Recent data substantiate the importance of acute gastroenteritis in the development of irritable bowel syndrome (IBS). An animal model of postinfectious IBS determined the importance of cytolethal distending toxin B (CdtB) during live Campylobacter jejuni infection and its development of autoimmunity to vinculin. In this study, we examine whether subcutaneous exposure to CdtB alone is sufficient to produce the postinfectious IBS effect and autoimmunity. Methods Sixty adult Sprague Dawley rats were randomized into 2 groups to receive subcutaneous injection of either CdtB or vehicle and administered a booster injection of the same product 3 weeks later. Serum was collected for anti-CdtB and anti-vinculin titers. Duodenal and ileal luminal contents for total eubacterial qPCR, and ileal bowel segments were harvested for vinculin and ileal expression. In a second experiment, 4 adult, Sprague Dawley rats were injected with either Cy7-labeled anti-CdtB and anti-vinculin antibodies were injected into the tail vein and imaged to determine organ localization of the antibodies. Key Results Rats that received CdtB increased in serum anti-CdtB after injection. CdtB exposure also precipitated significant elevation in anti-vinculin antibodies (P < .001). This was associated with a reduction in intestinal vinculin expression (P < .001) that negatively correlated with serum anti-CdtB levels. CdtB exposure was also associated with greater levels of duodenal (P < .001) and ileal (P < .01) bacteria by qPCR that positively correlated with anti-CdtB levels. Conclusions and Inferences Rats injected with CdtB developed a postinfectious IBS-like phenotype and autoimmunity to vinculin with corresponding reduction in intestinal vinculin expression.

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