Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus encephalitis |
| |
Authors: | Klein Robyn S Lin Eugene Zhang Bo Luster Andrew D Tollett Judy Samuel Melanie A Engle Michael Diamond Michael S |
| |
Institution: | Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. rklein@im.wustl.edu |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|