Abstract

Abstract West Nile Virus (WNV)-induced neuroinvasive disease (WNND) has been a public health concern in North America since its introduction in 1999. In recent years, severe neurological illness has been reported much more frequently, together with neuromuscular manifestations. Previous studies have shown that dendritic cells (DCs) within the central nervous system (CNS) are required to restrict WNV replication and immunopathology by regulating anti-viral T-cell responses. In this study, we examined the role of CMKLR1 within the CNS during WNV encephalitis. CMKLR1-expressing microglial cells and CNS-infiltrating myeloid DCs have been shown to have an inflammatory role during autoimmune neurological disorders, yet their contribution to WNND remains unknown. In addition, chemerin, the ligand for CMKLR1, was upregulated in the CNS of WNV-infected mice. To evaluate the role of CMKLR1, we infected CMKLR1-deficient (CMKLR1−/−) and wild-type (WT) mice with WNV. WNV-infected CMKLR1−/− mice exhibited increased susceptibility to WNV, loss of virologic control, and more severe clinical signs of disease. Proinflammatory chemokine expression, including CCL5, CXCL9, and CXCL10, was significantly decreased in the absence of CMKLR1 suggesting reduced leukocyte trafficking into the CNS. For future studies, we will determine the numbers and type of infiltrating leukocytes and their role in virologic control within the WNV-infected CNS. Taken together, these data will help clarify the immunoregulatory role of CMKLR1 during WNV encephalitis. NIH-SC3GM130472

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