CXCL10 is required for the recruitment of leukocytes responsible for controlling herpes simplex virus-1 infection (43.19)

Abstract

Abstract The chemokine CXCL10 is among the earliest cytokines produced during nervous system inflammation induced by herpes simplex virus-1 (HSV-1) infection. Current evidence suggests CXCL10 is important in the recruitment of a wide range of leukocytes including CD4 and CD8+ T-cells, macrophages, dendritic, and NK cells. Many of these studies have suggested the function of this chemokine extends beyond simple leukocyte recruitment as CXCL10 is also expressed in primary and secondary lymphoid tissues. To elucidate the role CXCL10 has in generating an effective immune response to viral infection of the nervous system, we have analyzed leukocyte recruitment and effector function in CXCL10 deficient (−/−) mice relative to wild type C57BL6/J, CXCL9 deficient, and CXCR3 deficient mice infected with HSV-1. Our results indicate CXCL10 is critical for the recruitment of NK cells and B220+CD11c+ cells, in a CXCR3-dependent manner. Infiltration of HSV-1 specific CD8+ T-cells into the central nervous system of CXCL10 −/− mice is significantly reduced compared to wild type mice, but CXCL10 expression in lymphoid tissues does not contribute in the generation of HSV-specific CD8+ T-cells. Nervous system restricted expression of CXCL10 restored the homing of HSV-1 specific CD8+ T-cells to wild type levels and partially restored homing of natural killer and conventional dendritic (B220-CD11c+) cells.