IFNγ regulates CXCL12 expression and cell trafficking during WNV infection (105.39)

Abstract

Abstract West Nile Virus (WNV), a mosquito-transmitted neurotropic flavivirus, causes severe neuroinvasive disease in the elderly and immuno-compromised. For viral clearance and survival, it is essential that virus-specific T cells enter into the central nervous system (CNS) parenchyma in both human and murine subjects. The chemokine CXCL12 is a potent immune factor that dictates homing and motility of lymphocytes to specific microenvironments. In the context of WNV encephalitis, we have shown that CXCL12-mediated localization of lymphocytes to the perivascular space modulates their ability to efficiently control infection. This localization regulates the parenchymal entry of infiltrating leukocytes during neuroinflammatory diseases. However, the means by which CXCL12 is regulated and how this regulation influences cell trafficking during WNV remains unclear. We show that CXCL12 is up-regulated within the spleen and down-regulated in the CNS on day 8 post-WNV infection. However, in the absence of IFN-γ, there is an increase in CXCL12 expression in the CNS of WNV-infected mice. We propose that during WNV infection, IFN-γ regulates CXCL12 expression both in the periphery and in the CNS, which has an effect on the localization of leukocytes and therefore influences the function of these cells to efficiently control infection.