Regulation of immune response and inflammatory reactions against viral infection by VCAM-1

Rong Ou, Menghua Zhang, Lei Huang, Richard A. Flavell, Pandelakis Koni, Dimitrios Moskofidis

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The migration of activated antigen-specific immune cells to the target tissues of virus replication is controlled by the expression of adhesion molecules on the vascular endothelium that bind to ligands on circulating lymphocytes. Here, we demonstrate that the adhesion pathway mediated by vascular cell adhesion molecule 1 (VCAM-1) plays a role in regulating T-cell-mediated inflammation and pathology in nonlymphoid tissues, including the central nervous system (CNS) during viral infection. The ablation of VCAM-1 expression from endothelial and hematopoietic cells using a loxP-Cre recombination strategy had no major effect on the induction or overall tissue distribution of antigen-specific T cells during a systemic infection with lymphocytic choriomeningitis virus (LCMV), except in the case of lung tissue. However, enhanced resistance to lethal LCM and the significantly reduced magnitude and duration of footpad swelling observed in VCAM-1 mutant mice compared to B6 controls suggest a significant role for VCAM-1 in promoting successful local inflammatory reactions associated with efficient viral clearance and even life-threatening immunopathology under particular infection conditions. Interestingly, analysis of the infiltrating populations in the brains of intracerebrally infected mice revealed that VCAM-1 deletion significantly delayed migration into the CNS of antigen-presenting cells (macrophages and dendritic cells), which are critical for optimal stimulation of migrating virus-specific CD8+ T cells initiating a pathological cascade. We propose that the impaired migration of these accessory cells in the brain may explain the improved clinical outcome of infection in VCAM-1 mutant mice. Thus, these results underscore the potential role of VCAM-1 in regulating the immune response and inflammatory reactions against viral infections.

Original languageEnglish (US)
Pages (from-to)2952-2965
Number of pages14
JournalJournal of Virology
Volume82
Issue number6
DOIs
StatePublished - Mar 1 2008

Fingerprint

Vascular Cell Adhesion Molecule-1
Virus Diseases
cell adhesion
blood vessels
immune response
infection
T-lymphocytes
T-Lymphocytes
Central Nervous System Viral Diseases
central nervous system
adhesion
Infection
mice
Lymphocytic choriomeningitis virus
Antigens
immunopathology
antigens
brain
Vascular Endothelium
Brain

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Regulation of immune response and inflammatory reactions against viral infection by VCAM-1. / Ou, Rong; Zhang, Menghua; Huang, Lei; Flavell, Richard A.; Koni, Pandelakis; Moskofidis, Dimitrios.

In: Journal of Virology, Vol. 82, No. 6, 01.03.2008, p. 2952-2965.

Research output: Contribution to journalArticle

Ou, Rong ; Zhang, Menghua ; Huang, Lei ; Flavell, Richard A. ; Koni, Pandelakis ; Moskofidis, Dimitrios. / Regulation of immune response and inflammatory reactions against viral infection by VCAM-1. In: Journal of Virology. 2008 ; Vol. 82, No. 6. pp. 2952-2965.
@article{9694e1de504f414497e7053c5a8cf851,
title = "Regulation of immune response and inflammatory reactions against viral infection by VCAM-1",
abstract = "The migration of activated antigen-specific immune cells to the target tissues of virus replication is controlled by the expression of adhesion molecules on the vascular endothelium that bind to ligands on circulating lymphocytes. Here, we demonstrate that the adhesion pathway mediated by vascular cell adhesion molecule 1 (VCAM-1) plays a role in regulating T-cell-mediated inflammation and pathology in nonlymphoid tissues, including the central nervous system (CNS) during viral infection. The ablation of VCAM-1 expression from endothelial and hematopoietic cells using a loxP-Cre recombination strategy had no major effect on the induction or overall tissue distribution of antigen-specific T cells during a systemic infection with lymphocytic choriomeningitis virus (LCMV), except in the case of lung tissue. However, enhanced resistance to lethal LCM and the significantly reduced magnitude and duration of footpad swelling observed in VCAM-1 mutant mice compared to B6 controls suggest a significant role for VCAM-1 in promoting successful local inflammatory reactions associated with efficient viral clearance and even life-threatening immunopathology under particular infection conditions. Interestingly, analysis of the infiltrating populations in the brains of intracerebrally infected mice revealed that VCAM-1 deletion significantly delayed migration into the CNS of antigen-presenting cells (macrophages and dendritic cells), which are critical for optimal stimulation of migrating virus-specific CD8+ T cells initiating a pathological cascade. We propose that the impaired migration of these accessory cells in the brain may explain the improved clinical outcome of infection in VCAM-1 mutant mice. Thus, these results underscore the potential role of VCAM-1 in regulating the immune response and inflammatory reactions against viral infections.",
author = "Rong Ou and Menghua Zhang and Lei Huang and Flavell, {Richard A.} and Pandelakis Koni and Dimitrios Moskofidis",
year = "2008",
month = "3",
day = "1",
doi = "10.1128/JVI.02191-07",
language = "English (US)",
volume = "82",
pages = "2952--2965",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "6",

}

TY - JOUR

T1 - Regulation of immune response and inflammatory reactions against viral infection by VCAM-1

AU - Ou, Rong

AU - Zhang, Menghua

AU - Huang, Lei

AU - Flavell, Richard A.

AU - Koni, Pandelakis

AU - Moskofidis, Dimitrios

PY - 2008/3/1

Y1 - 2008/3/1

N2 - The migration of activated antigen-specific immune cells to the target tissues of virus replication is controlled by the expression of adhesion molecules on the vascular endothelium that bind to ligands on circulating lymphocytes. Here, we demonstrate that the adhesion pathway mediated by vascular cell adhesion molecule 1 (VCAM-1) plays a role in regulating T-cell-mediated inflammation and pathology in nonlymphoid tissues, including the central nervous system (CNS) during viral infection. The ablation of VCAM-1 expression from endothelial and hematopoietic cells using a loxP-Cre recombination strategy had no major effect on the induction or overall tissue distribution of antigen-specific T cells during a systemic infection with lymphocytic choriomeningitis virus (LCMV), except in the case of lung tissue. However, enhanced resistance to lethal LCM and the significantly reduced magnitude and duration of footpad swelling observed in VCAM-1 mutant mice compared to B6 controls suggest a significant role for VCAM-1 in promoting successful local inflammatory reactions associated with efficient viral clearance and even life-threatening immunopathology under particular infection conditions. Interestingly, analysis of the infiltrating populations in the brains of intracerebrally infected mice revealed that VCAM-1 deletion significantly delayed migration into the CNS of antigen-presenting cells (macrophages and dendritic cells), which are critical for optimal stimulation of migrating virus-specific CD8+ T cells initiating a pathological cascade. We propose that the impaired migration of these accessory cells in the brain may explain the improved clinical outcome of infection in VCAM-1 mutant mice. Thus, these results underscore the potential role of VCAM-1 in regulating the immune response and inflammatory reactions against viral infections.

AB - The migration of activated antigen-specific immune cells to the target tissues of virus replication is controlled by the expression of adhesion molecules on the vascular endothelium that bind to ligands on circulating lymphocytes. Here, we demonstrate that the adhesion pathway mediated by vascular cell adhesion molecule 1 (VCAM-1) plays a role in regulating T-cell-mediated inflammation and pathology in nonlymphoid tissues, including the central nervous system (CNS) during viral infection. The ablation of VCAM-1 expression from endothelial and hematopoietic cells using a loxP-Cre recombination strategy had no major effect on the induction or overall tissue distribution of antigen-specific T cells during a systemic infection with lymphocytic choriomeningitis virus (LCMV), except in the case of lung tissue. However, enhanced resistance to lethal LCM and the significantly reduced magnitude and duration of footpad swelling observed in VCAM-1 mutant mice compared to B6 controls suggest a significant role for VCAM-1 in promoting successful local inflammatory reactions associated with efficient viral clearance and even life-threatening immunopathology under particular infection conditions. Interestingly, analysis of the infiltrating populations in the brains of intracerebrally infected mice revealed that VCAM-1 deletion significantly delayed migration into the CNS of antigen-presenting cells (macrophages and dendritic cells), which are critical for optimal stimulation of migrating virus-specific CD8+ T cells initiating a pathological cascade. We propose that the impaired migration of these accessory cells in the brain may explain the improved clinical outcome of infection in VCAM-1 mutant mice. Thus, these results underscore the potential role of VCAM-1 in regulating the immune response and inflammatory reactions against viral infections.

UR - http://www.scopus.com/inward/record.url?scp=40149106133&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40149106133&partnerID=8YFLogxK

U2 - 10.1128/JVI.02191-07

DO - 10.1128/JVI.02191-07

M3 - Article

C2 - 18216105

AN - SCOPUS:40149106133

VL - 82

SP - 2952

EP - 2965

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 6

ER -