Dendritic Cell-Based Therapeutic Immunization Induces Th1/Th17 Responses and Reduces Fungal Burden in Experimental Sporotrichosis

Abstract

Sporotrichosis is a globally distributed mycosis caused by thermally dimorphic fungi of the <i>Sporothrix schenckii</i> species complex. In Brazil, sporotrichosis is considered endemic and is usually acquired through zoonotic transmission from infected cats. The clinical manifestations may be cutaneous, lymphocutaneous, or systemic, the latter being more commonly observed in immunosuppressed patients. The limited effectiveness of antifungal treatments against this mycosis, particularly in immunocompromised individuals, has led to the search for more effective and safer therapies. Based on several studies demonstrating the efficient use of dendritic cells as tools for the development of antifungal vaccines, this work aimed to evaluate the protective capacity of bone marrow-derived dendritic cells (BMDCs) activated with cell wall proteins of <i>S. schenckii</i> (SsCWP) in mice infected with <i>S. schenckii sensu stricto</i>. BMDCs were stimulated with SsCWP and analyzed for the surface expression of costimulatory molecules as well as proinflammatory cytokine secretion. Subsequently, mice were vaccinated once or twice to assess immunogenicity, and finally, the therapeutic effect of BMDCs on <i>S. schenckii</i> infection was evaluated. Our results show that SsCWP was able to activate BMDCs. Immunization of healthy mice with SsCWP-stimulated BMDCs induced a balanced Th1/Th17-based immune response. Vaccination of mice previously infected with <i>S. schenckii</i> induced a mixed Th1/Th17 response and reduced fungal burden in the spleen. Overall, these findings demonstrate that therapeutic vaccination with SsCWP-stimulated BMDCs improves fungal control, supporting the notion that dendritic cells represent a promising therapeutic strategy against sporotrichosis.