CXCR3 Mediates Region-Specific Antiviral T Cell Trafficking within the Central Nervous System during West Nile Virus Encephalitis

Zhang, Bo; Chan, Ying; Liu, Bao; Diamond, Michael S.; Klein, Robyn S.

doi:10.4049/jimmunol.180.4.2641

Cited by 162 publications

(160 citation statements)

References 77 publications

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“…Using genetically deficient mice and antibody neutralization approaches, Klein and colleagues showed that CXCL10 is critical for the recruitment of CXCR3-expressing T cells into the CNS and survival from WNV infection in mice [25]. Likewise, genetic deficiency of CXCR3 recapitulated this phenotype [50,51]. Loss of either resulted in decreased T-cell recruitment to the CNS and increased viral burden and mortality.…”

Section: Cxcr3/cxcl10mentioning

confidence: 99%

The role of chemokines in the pathogenesis of neurotropic flaviviruses

Bardina

Lim

2012

Immunol Res

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Neurotropic flaviviruses are important emerging and reemerging arthropod-borne pathogens that cause significant morbidity and mortality in humans and other vertebrates worldwide. Upon entry and infection of the CNS, these viruses can induce a rapid inflammatory response characterized by the infiltration of leukocytes into the brain parenchyma. Chemokines and their receptors are involved in coordinating complex leukocyte trafficking patterns that regulate viral pathogenesis in vivo. In this review, we will summarize the current literature on the role of chemokines in regulating the pathogenesis of West Nile, Japanese encephalitis, and tick-borne encephalitis virus infections in mouse models and humans. Understanding how viral infections trigger chemokines, the key cellular events that occur during the infection process, as well as the immunopathogenic role of these cells, are critical areas of research that may ultimately guide a much needed effort toward developing specific immunomodulators and/or antiviral therapeutics.

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Section: Cxcr3/cxcl10mentioning

confidence: 99%

The role of chemokines in the pathogenesis of neurotropic flaviviruses

Bardina

Lim

2012

Immunol Res

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“…While these chemokines are not detectable in the healthy brain, their expression is highly upregulated following infection of the CNS with various viruses (2,3,10,21,23,24). Deficiency of CXCR3 has been associated with reduced trafficking to and/or positioning of T cells in the CNS in a number of different virally-induced disease models, such as West Nile virus encephalitis (45), mouse hepatitis virus encephalitis (43), and dengue virus encephalitis (18).…”

Section: Ymphocytic Choriomeningitis Virus (Lcmv) Is a Membermentioning

confidence: 99%

Unaltered Neurological Disease and Mortality in CXCR3-Deficient Mice Infected Intracranially with Lymphocytic Choriomeningitis Virus-Armstrong

et al. 2008

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Intracranial infection of mice with lymphocytic choriomeningitis virus (LCMV) results in a lethal neurological disease termed lymphocytic choriomeningitis (LCM) that is mediated by antiviral CD8 ϩ T cells. Previous studies have implicated the chemokine receptor CXCR3 and its ligand CXCL10 in CD8 ϩ T cell trafficking in the brain and in the lethal disease following intracranial infection of mice with the LCMV-Traub strain. Here we investigated the role of CXCR3 in LCM following intracranial infection of mice with the LCMV-Armstrong strain. Significant induction of both CXCL9 and CXCL10 RNA and protein was seen in the central nervous system (CNS) in LCM. Cellular localization of the CXCL9 and CXCL10 RNA transcripts was identified predominantly in infiltrating mononuclear cells, as well as in subpial and paraventricular microglia (CXCL9) and astrocytes (CXCL10). Despite a primary role of interferon (IFN)-␥ in inducing the expression of the CXCL9 gene, and to a lesser extent the CXCL10 gene in LCM, the absence of the IFN-␥ receptor did not influence the disease outcome. This finding suggested that these chemokines may not play a major role in the pathogenesis of LCM. To evaluate this possibility further the development of LCM was examined in mice that were deficient for CXCR3. Surprisingly, in the absence of CXCR3 there was no alteration in mortality, cytokine expression, or T cell infiltration in the CNS, demonstrating that in contrast to LCMV-Traub, CXCR3 is not involved in the pathogenesis of LCMV-Armstrong-induced neurological disease in mice. Our findings indicate that despite similar immunopathogenetic mechanisms involving antiviral CD8 ϩ T cells, whether or not CXCR3 signaling has a role in LCM is dependent upon the infecting strain of LCMV. 425

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“…Elimination of virus-infected cells in the CNS requires a CD8 T-cell response [233][234][235][236]. In response to WNVand JEV infections, neurons release CXCL10, which is required for recruitment of CD8 T cells into the brain via the C-X-C chemokine receptor (CXCR)3 [151,170].…”

Section: Viral Clearance From the Cnsmentioning

confidence: 99%

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

2016

Self Cite

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Arboviruses are arthropod-borne viruses that exhibit worldwide distribution, contributing to systemic and neurologic infections in a variety of geographical locations. Arboviruses are transmitted to vertebral hosts during blood feedings by mosquitoes, ticks, biting flies, mites, and nits. While the majority of arboviral infections do not lead to neuroinvasive forms of disease, they are among the most severe infectious risks to the health of the human central nervous system. The neurologic diseases caused by arboviruses include meningitis, encephalitis, myelitis, encephalomyelitis, neuritis, and myositis in which virus-and immune-mediated injury may lead to severe, persisting neurologic deficits or death. Here we will review the major families of emerging arboviruses that cause neurologic infections, their neuropathogenesis and host neuroimmunologic responses, and current strategies for treatment and prevention of neurologic infections they cause.

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CXCR3 Mediates Region-Specific Antiviral T Cell Trafficking within the Central Nervous System during West Nile Virus Encephalitis

Cited by 162 publications

References 77 publications

The role of chemokines in the pathogenesis of neurotropic flaviviruses

The role of chemokines in the pathogenesis of neurotropic flaviviruses

Unaltered Neurological Disease and Mortality in CXCR3-Deficient Mice Infected Intracranially with Lymphocytic Choriomeningitis Virus-Armstrong

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

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