Leishmania spp. are obligatory intracellular parasites that primarily infect macrophages. The macrophage immune response plays a pivotal role in determining the control or progression of infection. “M1-like” macrophages mediate parasite clearance through the production of nitric oxide, pro-inflammatory cytokines, and reactive oxygen species, whereas “M2-like” macrophages contribute to infection progression by exerting anti-inflammatory effects. The capsular polysaccharides Glucuronoxylomannan (GXM) and glucuronoxylomannogalactan (GXMGal) from Cryptococcus neoformans are capable of immunomodulating the macrophage response. GXM exhibits immunoregulatory activity, whereas GXMGal induces a pro-inflammatory response. Although the activity of these polysaccharides has been studied in cryptococcosis, their immunomodulatory potential in other infectious models remains largely unexplored. Here, we investigated the effects of GXM and GXMGal on Leishmania major infection in murine peritoneal macrophages. Murine peritoneal macrophages were infected with L. major and, 24 h post-infection, treated with 50 μg of either GXM or GXMGal. Our data revealed that GXM treatment enhanced L. major infection, while GXMGal treatment had no significant effect on the parasitic load in infected macrophages.

Cryptococcosis is a disease originating in the lungs, often seen in immunosuppressed patients. In severe cases, it can lead to meningoencephalitis and can be fatal. Biochemical studies have shown that the capsule of Cryptococcus neoformans is predominantly composed of glucuronoxylomannan (GXM), with glucuronoxylomannogalactan (GXMGal) present in smaller amounts. These polysaccharides have different effects on the immune system, with GXM mainly having anti-inflammatory properties, while GXMGal is more pro-inflammatory. Myeloid-derived suppressor cells (MDSCs) are a diverse group of immature myeloid cells, including progenitor cells and precursors of macrophages, granulocytes, and dendritic cells at different stages of development. MDSCs are known to suppress immune responses in various diseases, including bacterial and fungal infections, through mechanisms such as the inhibition of T cell proliferation. In this study, we show that infection with either B3501 or CAP67 strains results in the accumulation of granulocytic MDSC precursors in bronchoalveolar cavities. The MDSCs recruited by the B3501 strain suppress T cell proliferation, while those recruited by the CAP67 strain do not. Furthermore, we observed the expression of PD-L1 on these MDSCs, suggesting a potential mechanism of immunosuppression during infection. These findings reveal how the polysaccharides of C. neoformans might weaken the host’s immune defense.