Enhanced viral clearance and reduced leukocyte infiltration in experimental herpes encephalitis after intranasal infection of CXCR3-deficient mice

Autor: A. Dockhorn, Marius Krauthausen, Julian Zimmermann, Eva Lorentzen, Marcus Müller, Daniel R. Getts, Joachim E. Kühn, Nicholas J. C. King, Wali Hafezi
Rok vydání: 2017
Předmět:
0301 basic medicine
Chemokine
Receptors
CXCR3
chemical and pharmacologic phenomena
Herpesvirus 1
Human
Biology
CXCR3
medicine.disease_cause
Proinflammatory cytokine
Interferon-gamma
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Immune system
stomatognathic system
Cell Movement
Virology
Weight Loss
Leukocytes
medicine
Animals
Humans
Administration
Intranasal
Neuroinflammation
Disease Resistance
Mice
Knockout
Tumor Necrosis Factor-alpha
Brain
Viral Load
medicine.disease
Chemokine CXCL10
Mice
Inbred C57BL
Disease Models
Animal
stomatognathic diseases
030104 developmental biology
Herpes simplex virus
Gene Expression Regulation
Neurology
DNA
Viral
Immunology
biology.protein
Encephalitis
Herpes Simplex
Microglia
Neurology (clinical)
Viral load
030217 neurology & neurosurgery
Encephalitis
Zdroj: Journal of NeuroVirology. 23:394-403
ISSN: 1538-2443
1355-0284
DOI: 10.1007/s13365-016-0508-6
Popis: 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.
Databáze: OpenAIRE
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