IMMUNOMODULATORY ROLE OF CAPSULAR POLYSACCHARIDES (GXM OR GXMGAL) FROM CRYPTOCOCCUS NEOFORMANS IN MACROPHAGES INFECTED WITH LEISHMANIA MAJOR

Cryptococcus neoformans is a encapsulated yeast that causes infection in humans and animals. Its capsule, a crucial survival factor in the host, is mainly composed of two polysaccharides: glucuronoxylomannan (GXM) and glucuronoxylomannogalactan (GXMGal). In the literature and in experiments from our group, it has been observed that these polysaccharides exhibit immunomodulatory actions in different types of cells, such as macrophages. GXM primarily exerts an immunoregulatory activity, inducing an anti-inflammatory response profile and leading to an increase in anti-inflammatory cytokines like IL-10. On the other hand, GXMGal predominantly has an immune-activating activity, acting as an inducer of a pro-inflammatory response, which results in increased levels of pro-inflammatory molecules such as TNF-α and nitric oxide. The immunomodulatory activity of these polysaccharides could be relevant in the context of pathologies. Therefore, we decided to investigate the role of these polysaccharides in peritoneal macrophages, CEUA 079/19,  infected with Leishmania major (L. major), as macrophages are the primary host cells for these parasites and the response profile of these cells is important for the resolution or maintenance of the infection. The first objective was to analyze the parasitic load of the extracellular form of L. major (promastigotes) in macrophages treated with GXM or GXMGal in the presence or absence of IFN-γ. As a result, we observed an increase in parasitic load in cells treated with GXM, but not with GXMGal. Based on this, we assessed the macrophage response profile by measuring PGE2, nitric oxide, cytokines such as IL-10, TNF-α, and TGF-β, and quantifying lipid bodies. Our data revealed that GXM increases the anti-inflammatory response of macrophages, contributing to the worsening of L. major infection.