Journal
JOURNAL OF CROHNS & COLITIS
Volume 6, Issue 4, Pages 454-463Publisher
OXFORD UNIV PRESS
DOI: 10.1016/j.crohns.2011.09.015
Keywords
Crohn's disease; Herpes simplex virus; Viral infection; IL-6; IFN-beta
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Funding
- Crohn's and Colitis Foundation of Canada
- Canadian Institutes of Health Research CIHR Team in Immunoregulation [IIN - 84037]
- Canadian Foundation for Innovation
- Canadian Association of Gastroenterology/Axcan Pharma
- Canada Research Chair in Immune-Mediated Gastrointestinal Disorders
- IBD at McGill
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The exogenous triggers responsible for Crohn's disease (CD) relapses are not often identified. Cytomegalovirus and other members of the herpesvirus family have been implicated in precipitating relapses. However, the role of viral infections in the immunopathogenesis of CD remains poorly understood. We describe an ex-vivo model of primary viral infection of CD tissue with Herpes Simplex Virus type I (HSV-1). IL-6 and CD68 served as markers for CD inflammation, type I IFNs for viral infection. Colonic explants obtained from CD resections were infected via the luminal or the submucosal compartments with HSV-1 or mock virus solution, at varying concentrations for up to 20 h. Serial tissue sections were assayed for expression of HSV-1 specific antigens, CD-68, IL-6 and DC-SIGN. Culture supernatants were tested for IL-6 and type I IFN production. Positive immunostaining for HSV-1 specific antigens was consistently detectable using 11 x 10(6) PFU from 13 h onwards, mainly on cells located in the submucosa, and in the perivascular area. CD68 was up-regulated in lamina propria macrophages from mildly and non-inflamed CD tissue after HSV-1 infection. IL-6+ cells in the infected tissues were mainly submucosal DC-SIGN+ dendritic cells. IL-6 and IFN-beta levels were higher in the supernatants from HSV-1-infected explants compared to controls after 20 h of culture (p<0.01). These data show increased expression of inflammatory markers during the initial stages of HSV-1 primary infection using CD colonic explants. This in vitro model appears promising to study the immunoregulatory changes induced by microbial infection in reactivation of CD. (C) 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
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