Sa1756 Co-Infection With an Intestinal Helminth Exacerbates Salmonella Enterocolitis in Mice

Abstract

Background and Aim:Murine norovirus (MNV) infection was shown to induce histopathological changes in the intestine of conventional housed mice or lethal systemic infection in immunocompromised mice. The mechanism which triggered the inflammation is not well understood. In the present study, the influence of MNV infection on histological and immunological characteristics of mucosal inflammation in germfree and Schaedler flora colonized IL10-deficient (Il10-/-) mouse model was examined. Methods: Germfree (GF) C57Bl/6J-Il10-/mice and GF mice colonized with Schaedler Flora were monitored after MNV infection for structural and functional intestinal barrier changes using histology, RTqPCR, ELISA and TUNEL assay. Results: No inflammatory lesions were observed in GF B6Il10-/and MNV-infected mice whereas in MNV-infected GF mice colonized with Schaedler Flora inflammatory lesions were detected comparable to SPF mice infected with MNV. Interferon inducible genes were increased in the small intestine of GFmice 48h after infection. However, four weeks after infection GF mice showed no increased IFNgamma production, whereas in Schaedler Flora colonized mice IFNgamma production was increased similar to SPF infected mice. Although there is no reduction of gene expression of tight junction molecules and an enhanced rate of epithelial apoptosis 48h after infection of GF mice the expression level changed within 4 weeks in MNV infected Schaedler Flora. Conclusions: MNV induces inflammation and epithelial barrier disruption that depends on the presence of the bacteria. Thus, MNV and enteric microbiota together represent a potent colitogenic stimulus and inflammatory trigger.