Modulation of Feline Macrophage Microbicidal Activity by Cryptococcus neoformans and its Capsular Polysaccharides

Cryptococcus neoformans is an fungus that causes cryptococcosis, a multisystemic disease affecting many mammals. In felines, the infection manifests as granulomatous rhinitis and can involve the central nervous system. The fungal capsule is the primary virulence factor, conferring resistance to phagocytosis and modulating the immune system. Macrophages are essential of both innate and adaptive immunity and play a crucial role in defense against the pathogen, although C. neoformans can survive intracellularly and utilize these cells as a vehicle for dissemination. This study evaluated the inhibition of feline macrophage microbicidal activity by the fungus and its polysaccharides. Feline macrophages (Fcwf-4) were cultured in the presence of strains B3501, Cap67, glucuronoxylomannan (GXM) or glucuronoxylomannogalactan (GXMGal). The results showed that encapsulated B3501 yeasts inhibited phagocytosis by Fcwf-4 macrophages compared with acapsular Cap67 yeasts. Similarly, purified capsular polysaccharides significantly inhibited phagocytosis. The analysis of key molecules involved in yeast clearance and inflammatory response, showed that the production of reactive oxygen species (ROS) was affected by B3501, Cap67 yeasts, GXM and GXMGal. We also evaluated nitric oxide (NO) production. Interestingly, the presence of B3501 yeasts inhibited NO production, whereas Cap67 yeasts did not. However, a significant reduction in NO production was observed in the presence of GXM and GXMGal. These results suggest that the capsule and its purified polysaccharides are capable of inhibiting phagocytosis by feline Fcwf-4 macrophages, an effect not observed with the acapsular strain. The inhibition of ROS and NO production by the B3501 strain and the polysaccharides reinforces their modulatory effect on feline macrophages, indicating that, under the influence of these components, these phagocytes might be less effective at eliminating the yeast and inducing an inflammatory response.