Glucuronoxylomannan (GXM) modulates macrophage proliferation and apoptosis through the STAT1 signaling pathway.

cryptococcus neoformans (C. neoformans) is a crucial opportunistic fungus that possesses an encapsulated fungal pathogen. The cryptococcal capsule is mainly composed of the polysaccharide glucuronoxylomannan (GXM). Macrophages form the first-line innate defense against cryptococcosis; however, the underlying mechanism remains unclear. In this study, GXM-treated RAW264.7 macrophages showed a notably reduced survival rate and increased apoptosis, accompanied by the promoted inducible nitric oxide synthase (iNOS) expression and NO production. Signal transducer and activator of transcription 1 (STAT1) expression was also found to be directly proportional to GXM concentration; STAT1 knockdown could alleviate GXM-induced proliferation decrease and apoptosis increase of macrophages, as well as reduce M1 polarization, iNOS expression and NO release. In conclusion, this study concluded that GXM was the main virulence factor of C. neoformans, which is critical in determining the mechanism of GXM-mediated protective immune response postinfection. The STAT1 signal pathway mediates the effect of GXM stimulation on macrophages, potentially providing a reference for further understanding the biological role of GXM.