Extracellular Vesicles from Dendritic Cells Protect Against Sporothrix brasiliensis Yeast Cells

Sporotrichosis is an emerging subcutaneous mycotic zoonosis that affects the skin, lymphatic system, and other organs of humans and animals. Like other infectious fungal diseases, it becomes even more severe when it affects immunosuppressed patients. This infection has a global distribution and is endemic in some regions of Brazil and it is an important zoonotic public health problem. The disease is caused by a complex of at least four pathogenic species, including Sporothrix brasiliensis. The immunological response against these species has not yet been completely elucidated. Still, structures such as extracellular vesicles could carry important components that can contribute to the modulation and control of this significant infection. Thus, this work aims to analyze the participation of EVs from naïve dendritic cells and EVs from DCs previously primed with S. brasiliensis yeast and primed with EVs from the fungus in the immune response against experimental sporotrichosis in murine models. The groups that received EVs from DCs primed with S. brasiliensis or their EVs showed a significant decrease in fungal load compared to the negative control group. When we analyzed the cytokine profile in the skin of mice treated with EVs before infection, we observed an increase in IFN-ℽ, TNF-α, IL-17, and IL-10, mainly in animals previously treated with EVs from DCs cultivated with yeast cells. It is worth highlighting that all prophylactic protocols modulated and minimized fungal growth compared to the control; that is, EVs contributed to the control of the infection and acted in favor of the host, demonstrating a protective character.