A comparative analysis of the dendritic cell response upon exposure to different rabies virus strains

Rabies is a viral zoonotic disease that causes over 60,000 human deaths annually worldwide. Natural infections lack a virus-specific immune response, leading to a near 100% fatality rate unless immediately treated. Rabies virus (RABV) is typically transmitted through bites from rabid dogs or other carnivores to humans and may initially interact with innate immune cells such as dendritic cells at the site of infection. This study investigates the in vitro response of human monocyte-derived dendritic cells (moDCs) exposed to two pathogenic RABV strains-silver-haired bat rabies virus (SHBRV) and dog-related rabies virus (dogRV)-and an attenuated vaccine strain (SAD P5). MoDCs were susceptible only to high doses of SHBRV and SAD P5, resulting in a more mature and migratory phenotype within the infected moDC populations. No infection was observed in moDCs exposed to dogRV. In co-culture with T cells, the presence of RABV-exposed moDCs, regardless of the strain, did not enhance T cell activation. Additionally, RABV exposure did not hinder LPS-induced moDC maturation; instead, high doses of SHBRV and SAD P5 even boosted activation levels. Overall, the findings suggest varied capabilities of RABV strains to infect and activate moDCs in vitro. However, exposure to any RABV strain did not provoke a clear antiviral state or suppression of moDC responsiveness. This lack of activation may contribute to the absence of an effective adaptive immune response in natural RABV infections.