Neuronal CXCL10 Directs CD8 + T-Cell Recruitment and Control of West Nile Virus Encephalitis
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The activation and entry of antigen-specific CD8 + T cells into the central nervous system is an essential step towards clearance of West Nile virus (WNV) from infected neurons. The molecular signals responsible for the directed migration of virus-specific T cells and their cellular sources are presently unknown. Here we demonstrate that in response to WNV infection, neurons secrete the chemokine CXCL10, which recruits effector T cells via the chemokine receptor CXCR3. Neutralization or a genetic deficiency of CXCL10 leads to a decrease in CXCR3 + CD8 + T-cell trafficking, an increase in viral burden in the brain, and enhanced morbidity and mortality. These data support a new paradigm in chemokine neurobiology, as neurons are not generally considered to generate antiviral immune responses, and CXCL10 may represent a novel neuroprotective agent in response to WNV infection in the central nervous system.
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Neuron-derived inflammatory signaling is a critical feature of the antiviral response to neurotropic viral infections.
“However, work examining the immune response to neurotropic viral infections reveals neuron‐derived inflammatory signaling is a critical feature of the antiviral response (Klein et al, 2005; Chakraborty et al, 2010; Di Liberto et al, 2018).”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Klein et al, 2005
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- Authors
- Klein, R. S., Lin, E., Zhang, B., Luster, A. D., Tollett, J., Samuel, M. A., Engle, M., & Diamond, M. S.
- Affiliations
- Washington University in St. Louis (US)
- Division of Infectious Diseases, Department of Medicine
- Massachusetts General Hospital (US)
- Corresponding author
- Klein, Robyn S.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2005-09
- Volume
- 79
- Issue
- 17
- Pages
- 11457-11466
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC1193600
- OpenAlex
- W2142913420
- Cited by
- 424
- References
- 65
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 22 · 2023: 17 · 2022: 13 · 2021: 18 · 2020: 19 · 2019: 24 · 2018: 15 · 2017: 21 · 2016: 14 · 2015: 24 · 2014: 30 · 2013: 31 · 2012: 18
- FWCI
- 9.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Edward Mallinckrodt, Jr. Foundation
- National Institutes of Health (5r01ca069212-18)
- National Cancer Institute (R01-CA069212)
- National Institute of Neurological Disorders and Stroke (K02NS045607, R01NS052632)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- West Nile virus, encephalitis, CXCL10, CXCR3, CD8+ T cells, T cell migration, chemokines, neuroinflammation, neuroprotection, viral encephalitis, antiviral immunity
- MeSH terms
- Animals, Cell Movement, Mice, Inbred C57BL, Neurons, T-Lymphocytes, West Nile Fever, West Nile virus, CD8 Antigens, Mice, Knockout, Receptors, Chemokine, Chemokines, CXC, Mice, Chemokine CXCL10, Receptors, CXCR3
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