<i>Cryptococcus neoformans</i> serotype A virulence and pathogenicity are capsular glucuronoxylomannan (GXM) motif composition dependent

Cryptococcosis is a systemic fungal infection that causes approximately 1 million cases globally, leading to approximately 625,000 annual deaths. Two species are responsible for the majority of cases, <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>. <i>C. neoformans</i> usually causes disease in immunosuppressed hosts, whereas <i>C. gattii</i> can infect and cause disease in immunocompetent hosts. The capsule of <i>Cryptococcus</i> spp. is one of its major virulence factors, due to its immunomodulation abilities. The capsule is composed of three major different molecules: glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoproteins. GXM is composed of six different structures called motifs. The exact mechanism and structures associated with its immunomodulation are still not well elucidated. Here, we looked at different immune responses based on the capsule composition. Our results strongly suggest that the capsule motif composition can affect the virulence, pathogenicity, and immunomodulatory capabilities of the <i>Cryptococcus</i> capsule.