Polymorphonuclear Myeloid-Derived Suppressor Cell Accumulation as a Response to Cryptococcus neoformans Infection

Cryptococcosis is a disease that originates in the lungs and is prevalent among immunosup-pressed individuals. In severe cases, it can lead to meningoencephalitis and even death. Bio-chemical studies have revealed that the capsule of this fungus is primarily composed of glucu-ronoxylomannan (GXM), which constitutes the majority of the capsule, while glucuronoxylo-mannogalactan (GXMGal) is present in smaller amounts. Previous studies have demonstrated that polysaccharide components exhibit different immunomodulatory activities. While GXM primarily exerts an anti-inflammatory effect, GXMGal conversely demonstrates greater pro-inflammatory activity. Myeloid-derived suppressor cells (MDSCs) encompass a heterogeneous population of immature myeloid cells, comprising myeloid progenitor cells and precursors of macrophages, granulocytes, and dendritic cells at various stages. It has been observed that MDSC populations contribute to negatively regulating the immune system in numerous pathol-ogies, such as bacterial and fungal infections, through mechanisms such as the inhibition of T lymphocyte proliferation. Here, we demonstrate that infection with either B3501 or CAP67 strains induced the accumulation of granulocytic precursors of myeloid-derived suppressor cells (MDSCs) in peritoneal and bronchoalveolar cavities. While the MDSCs recruited by the B3501 strain exhibit suppressive action on T lymphocytes, those recruited by the CAP67 strain could not suppress T lymphocyte proliferation. Additionally, we observed the presence of the pro-grammed death ligand PD-L1 in recruited MDSCs, indicating that this may represent a form of immunosuppression in this infection. These findings uncover a mechanism by which capsule polysaccharides from C. neoformans might compromise host immune responses.