Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus encephalitis.
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.
Klein
Robyn S
RS
Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. rklein@im.wustl.edu
Lin
Eugene
E
Zhang
Bo
B
Luster
Andrew D
AD
Tollett
Judy
J
Samuel
Melanie A
MA
Engle
Michael
M
Diamond
Michael S
MS
D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism; D002465:Cell Movement; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000276:immunology* / Q000821:virology; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014901:West Nile Fever / Q000276:immunology*; D014902:West Nile virus / Q000276:immunology*
D016827:CD8 Antigens; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine