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Enhanced viral clearance and reduced leukocyte infiltration in experimental herpes encephalitis after intranasal infection of CXCR3-deficient mice.
Zimmermann, J; Hafezi, W; Dockhorn, A; Lorentzen, Eva U; Krauthausen, M; Getts, Daniel R; Müller, M; Kühn, Joachim E; King, Nicholas J C.
Afiliação
  • Zimmermann J; Department of Neurology, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
  • Hafezi W; University Hospital Münster, Institute of Medical Microbiology-Clinical Virology, Münster, Germany.
  • Dockhorn A; Department of Neurology, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
  • Lorentzen EU; University Hospital Münster, Institute of Medical Microbiology-Clinical Virology, Münster, Germany.
  • Krauthausen M; Department of Neurology, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
  • Getts DR; Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Müller M; Cour Pharmaceutical Development Company, Elmhurst, IL, USA.
  • Kühn JE; The Discipline of Pathology, School of Medical Sciences, The University of Sydney, Sydney, NSW, 2006, Australia.
  • King NJC; Department of Neurology, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany. marcus_mathias_mueller@ukb.uni-bonn.de.
J Neurovirol ; 23(3): 394-403, 2017 06.
Article em En | MEDLINE | ID: mdl-28116674
Herpes simplex virus type 1 (HSV-1) encephalitis (HSE) is the most common fatal sporadic encephalitis in developed countries. There is evidence from HSE animal models that not only direct virus-mediated damage caused but also the host's immune response contributes to the high mortality of the disease. Chemokines modulate and orchestrate this immune response. Previous experimental studies in HSE models identified the chemokine receptor CXCR3 and its ligands as molecules with a high impact on the course of HSE in mouse models. In this study, the role of the chemokine receptor CXCR3 was evaluated after intranasal infection with the encephalitogenic HSV-1 strain 17 syn+ using CXCR3-deficient mice (CXCR3-/-) and wild-type controls. We demonstrated a neurotropic viral spread into the CNS of after intranasal infection. Although viral load and histological distribution of infected neurons were independent from CXCR3 signaling early after infection, CXCR3-deficient mice cleared HSV-1 more efficiently 14 days after infection. Furthermore, CXCR3 deficiency led to a decreased weight loss in mice after HSV-1 infection. T cell infiltration and microglial activation was prominently reduced by inhibition of CXCR3 signaling. Quantitative PCR of proinflammatory cytokines and chemokines confirmed the reduced neuroinflammatory response in CXCR3-deficient mice during HSE. Our results demonstrate that the recruitment of peripheral immune cells into the CNS, induction of neuroinflammation, and consecutive weight loss during herpes encephalitis is modulated by CXCR3 signaling. Interruption of the CXCR3 pathway ameliorates the detrimental host immune response and in turn, leads paradoxically to an enhanced viral clearance after intranasal infection. Our data gives further insight into the role of CXCR3 during HSE after intranasal infection.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Herpesvirus Humano 1 / Encefalite por Herpes Simples / Receptores CXCR3 / Resistência à Doença Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Herpesvirus Humano 1 / Encefalite por Herpes Simples / Receptores CXCR3 / Resistência à Doença Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article