Langerhans cells as targets of rabies virus immune evasion.

Rabies virus (RABV) is a neurotropic virus of the genus Lyssavirus that causes a nearly always fatal encephalitis in humans once it reaches the central nervous system. Dog bites are a major transmission route of RABV, and following superficial skin exposure, RABV first encounters epidermal Langerhans cells (LCs), yet their role in early infection remains poorly understood. Here, we show that exposure of immature human epidermal LCs to RABV leads to RABV association with cells in the absence of productive viral replication. RABV-exposed LCs display reduced cytokine and type I IFN responses and lack induction of IFN-stimulated genes, indicating suppression of antiviral signalling pathways. Together, these findings suggest that RABV is efficiently taken up by immature LCs, which dampens the antiviral immune responses of LCs, potentially facilitating immune evasion at the skin entry site.