Immunoregulation in Fungal Infections: A Review and Update on the Critical Role of Myeloid-Derived Suppressor Cells

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immune cells that play a central role in regulating host immune responses during fungal infections. Their recruitment is mediated by pathogen recognition receptors, particularly Dectin-1 and CARD9 signaling, which promote the production of reactive oxygen species (ROS) and IL-1β. Once activated, MDSCs suppress T-cell and natural killer cell functions through immunosuppressive cytokines like IL-10 and TGF-β, as well as enzymes such as arginase-1 and indoleamine 2,3-dioxygenase 1 (IDO-1). This review explores the role of MDSCs in fungal infections caused by Candida spp., Paracoccidioides brasiliensis, Aspergillus spp., and Cryptococcus neoformans, emphasizing their impact on immune modulation and disease progression. The emerging evidence suggests that fungal bioactive compounds, such as polysaccharides, can influence MDSC activity and restore immune balance. Notably, therapies targeting MDSCs have demonstrated promise in both fungal infections. In particular, infections with P. brasiliensis and C. neoformans show improved T-cell responses following MDSC-targeted interventions. Additionally, polysaccharides from Grifola frondosa and exposure to Aspergillus sydowii affect MDSC behavior, supporting the potential of modulating these cells therapeutically. Together, these findings highlight the relevance of MDSCs in fungal pathogenesis and underscore their potential as targets for immunotherapeutic strategies in infectious diseases.