title: Herpes simplex virus-1 infection of colonic explants as a model of viral-induced activation of Crohn's disease.
abstract: 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 11×10(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-β 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.
authors.affiliation: Sainte-Justine Hospital Research Center, Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Silva
authors.forename: José
authors.initials: J
authors.lastname: Menezes
authors.forename: Serge
authors.initials: S
authors.lastname: Dionne
authors.forename: Emile
authors.initials: E
authors.lastname: Levy
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Amre
authors.forename: Ernest G
authors.initials: EG
authors.lastname: Seidman
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D003106:Colon / Q000821:virology*; D003424:Crohn Disease / Q000276:immunology / Q000821:virology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006561:Herpes Simplex; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008297:Male; D014775:Virus Activation / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C063411:CD76 antigen; D016207:Cytokines; D015850:Interleukin-6