DEC-205+ dendritic cells strengthen barriers to shield the CNS and combat West Nile virus neuroinvasive disease 4574

Abstract Description West Nile Virus (WNV), a mosquito-borne flavivirus, often causes severe West Nile Neuroinvasive Disease (WNND), leading to encephalitis or meningitis, with no approved vaccines or specific treatments available. Dendritic cells (DCs) expressing the endocytic receptor DEC-205 are critical in conferring protection against WNND. Our studies demonstrate that DEC-205 knockout (DEC-205-/-) mice exhibit higher viral burdens in peripheral tissues, earlier neuroinvasion, and more severe neuropathology compared to wild-type (WT) mice. In contrast, WT mice display DEC-205+ DC localization at the blood-brain barrier (BBB), which is associated with reduced viral replication, decreased neuropathology, and limited immune cell trafficking into the central nervous system (CNS). Despite these findings, the mechanisms by which DEC-205+ DCs regulate viral entry and modulate immune responses in the CNS remain unclear. To address this, we analyzed early interactions between DEC-205+ DCs and T cells in draining lymph nodes to evaluate their role in establishing a barrier to CNS invasion. Furthermore, we are investigating how DEC-205+ DCs interact with other cells that maintain the BBB during WNND. Our research highlights the critical role of DEC-205+ DCs in mitigating viral replication and neuropathology during WNV infection by fortifying the BBB. These findings may inform the development of innovative therapeutic strategies for neurotropic viral infections. Funding Sources NIH - SC3GMI30472, NIH - T32GM137812 Topic Categories Neuroimmunology (NEUR)