Herpes simplex virus-1 infection of colonic explants as a model of viral-induced activation of Crohn's disease

Manuel A. Silva, José Menezes, Serge Dionne, Emile Levy, Devendra K. Amre, Ernest G. Seidman

Research output: Contribution to journalArticle

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 20h. 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 11×106PFU from 13h 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 20h 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.

Original languageEnglish (US)
Pages (from-to)454-463
Number of pages10
JournalJournal of Crohn's and Colitis
Volume6
Issue number4
DOIs
StatePublished - May 2012
Externally publishedYes

Fingerprint

Virus Activation
Human Herpesvirus 1
Virus Diseases
Crohn Disease
Interleukin-6
Infection
Antigens
Recurrence
Herpesviridae
Simplexvirus
Cytomegalovirus
Dendritic Cells
Mucous Membrane
Macrophages
Viruses
Inflammation

Keywords

  • Crohn's disease
  • Herpes simplex virus
  • IFN-β
  • IL-6
  • Viral infection

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Herpes simplex virus-1 infection of colonic explants as a model of viral-induced activation of Crohn's disease. / Silva, Manuel A.; Menezes, José; Dionne, Serge; Levy, Emile; Amre, Devendra K.; Seidman, Ernest G.

In: Journal of Crohn's and Colitis, Vol. 6, No. 4, 05.2012, p. 454-463.

Research output: Contribution to journalArticle

Silva, Manuel A. ; Menezes, José ; Dionne, Serge ; Levy, Emile ; Amre, Devendra K. ; Seidman, Ernest G. / Herpes simplex virus-1 infection of colonic explants as a model of viral-induced activation of Crohn's disease. In: Journal of Crohn's and Colitis. 2012 ; Vol. 6, No. 4. pp. 454-463.
@article{408eea9031e743feb30be758594f310f,
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 20h. 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 11×106PFU from 13h 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 20h 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.",
keywords = "Crohn's disease, Herpes simplex virus, IFN-β, IL-6, Viral infection",
author = "Silva, {Manuel A.} and Jos{\'e} Menezes and Serge Dionne and Emile Levy and Amre, {Devendra K.} and Seidman, {Ernest G.}",
year = "2012",
month = "5",
doi = "10.1016/j.crohns.2011.09.015",
language = "English (US)",
volume = "6",
pages = "454--463",
journal = "Journal of Crohn's and Colitis",
issn = "1873-9946",
publisher = "Elsevier",
number = "4",

}

TY - JOUR

T1 - Herpes simplex virus-1 infection of colonic explants as a model of viral-induced activation of Crohn's disease

AU - Silva, Manuel A.

AU - Menezes, José

AU - Dionne, Serge

AU - Levy, Emile

AU - Amre, Devendra K.

AU - Seidman, Ernest G.

PY - 2012/5

Y1 - 2012/5

N2 - 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 20h. 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 11×106PFU from 13h 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 20h 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.

AB - 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 20h. 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 11×106PFU from 13h 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 20h 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.

KW - Crohn's disease

KW - Herpes simplex virus

KW - IFN-β

KW - IL-6

KW - Viral infection

UR - http://www.scopus.com/inward/record.url?scp=84860207234&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860207234&partnerID=8YFLogxK

U2 - 10.1016/j.crohns.2011.09.015

DO - 10.1016/j.crohns.2011.09.015

M3 - Article

C2 - 22398063

AN - SCOPUS:84860207234

VL - 6

SP - 454

EP - 463

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

SN - 1873-9946

IS - 4

ER -