Cannabidiol promotes fine-tuning of natural killer and monocytic cells subsets as well as cytokine storm during chikungunya virus exposure in vitro: Insights for putative therapeutic interventions

Chikungunya virus (CHIKV) is an arbovirus that causes acute and chronic disease by strong stimulation of the immune system. It activates innate and adaptive immune cells, including monocytes, natural killer (NK) cells, and lymphocytes, as well as soluble mediators such as IL-17A, IFN-γ, IL-13, and IL-7. Despite the significant morbidity associated with CHIKV, no specific antiviral therapy is currently available. In this context, natural compounds with immunomodulatory potential, such as cannabidiol (CBD), represent promising candidates. Here, we investigated whether CBD modulates immune responses following CHIKV stimulation. Peripheral blood mononuclear cells (PBMCs) were stimulated with inactivated CHIKV and treated with CBD. Immune cell subsets were analyzed by flow cytometry, and soluble factors were profiled by Luminex assay. CBD treatment fine-tuned NK and monocyte subsets in vitro and attenuated key inflammatory pathways, particularly the IL-17A-IFN-γ axis, in response to CHIKV stimulation. These findings identify CBD as a potential immunomodulatory candidate for innovative therapeutic strategies against CHIKV and other alphaviruses.