Abstract

The chemokine CXCL10 exerts antiviral effects within the central nervous system (CNS) through the recruitment of virus-specific T cells. However, elevated levels of CXCL10 may induce neuronal apoptosis given its receptor, CXCR3, is expressed by neurons. Using a murine model of West Nile virus (WNV) encephalitis, we determined that WNV-infected neurons express TNF-α, which down-regulates neuronal CXCR3 expression via signaling through TNFR1. Down-regulation of neuronal CXCR3 decreased CXCL10-mediated calcium transients and delayed Caspase 3 activation. Loss of CXCR3 activation, via CXCR3-deficiency or pretreatment with TNF-α prevented neuronal apoptosis during in vitro WNV infection. These results suggest that neuronal TNF-α expression during WNV encephalitis may be an adaptive response to diminish CXCL10-induced death.

Original languageEnglish
Pages (from-to)28-38
Number of pages11
JournalJournal of Neuroimmunology
Volume224
Issue number1-2
DOIs
StatePublished - Jul 2010

Keywords

  • CNS
  • CXCL10
  • CXCR3
  • Neurons
  • TNF-α
  • West Nile virus

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