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

Summary

Researchers developed a vaccine using special immune cells called dendritic cells loaded with proteins from the fungus that causes sporotrichosis. When vaccinated mice were later infected with the fungus, they showed stronger immune responses and had lower levels of the fungus in their bodies. This suggests that dendritic cell-based vaccines could be a promising new treatment approach for sporotrichosis, a serious fungal infection that is difficult to treat with current medicines, especially in people with weakened immune systems.

Background

Sporotrichosis is a globally distributed mycosis caused by Sporothrix schenckii, endemic in Brazil with zoonotic transmission from infected cats. Limited effectiveness of current antifungal treatments, particularly in immunocompromised individuals, has prompted investigation of immunotherapeutic approaches. Dendritic cells have shown promising potential as platforms for developing antifungal vaccines due to their role in bridging innate and adaptive immunity.

Objective

To evaluate the protective capacity of bone marrow-derived dendritic cells (BMDCs) activated with S. schenckii cell wall proteins (SsCWP) in mice infected with S. schenckii sensu stricto. The study assessed whether therapeutic vaccination with SsCWP-stimulated BMDCs could induce protective immune responses and reduce fungal burden.

Results

SsCWP successfully activated BMDCs, increasing expression of costimulatory molecules (CD83, CD80, CD86, CD40) and proinflammatory cytokine production (TNF-α, IL-1β, IL-6, IL-12). Immunization induced balanced Th1/Th17 responses, with single-dose immunization showing stronger responses than double-dose. In infected mice, BMDC vaccination significantly reduced fungal burden in the spleen and promoted mixed Th1/Th17 immune responses.

Conclusion

Therapeutic vaccination with SsCWP-stimulated BMDCs effectively improved fungal control in experimental sporotrichosis by inducing protective Th1/Th17 immune responses. These findings support dendritic cells as a promising therapeutic platform for developing next-generation antifungal vaccines against sporotrichosis and potentially other systemic mycoses.
  • Published in:Microorganisms,
  • Study Type:Experimental Study,
  • Source: 10.3390/microorganisms13102351, PMID: 41156812
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