Abstract / Summary
Paracoccidioidomycosis (PCM) is a neglected tropical disease and the most prevalent systemic mycosis in Latin America. Infection is caused by thermally dimorphic fungi of the genus Paracoccidioides, and disease outcome is largely determined by the nature of the host immune response. Among the pattern recognition receptors involved in fungal sensing, the C-type lectin receptors (CLRs) Dectin-1, Dectin-2, and Dectin-3 are critical regulators of antifungal immunity through their recognition of fungal cell wall polysaccharides and activation of Syk-CARD9-dependent signaling pathways. This review summarizes current knowledge regarding the roles of these receptors in immunity to Paracoccidioides. Evidence from murine and human studies shows Dectin-1 and Dectin-2 as major innate sensors that promote fungal control by enhancing phagocyte function, inflammasome activation, and protective adaptive immune responses. In contrast, Dectin-3 demonstrates cell-type and species-specific relevance. The review further discusses fungal immune evasion strategies and Dectin-1 signaling in non-classical phagocytes, with implications for PCM immunopathology and chronicity. Finally, we evaluate emerging translational opportunities, including CLR-targeted vaccine adjuvants, receptor-directed immunotherapies, and Dectin-based antifungal drug-delivery platforms.