Cryptococcus gattii evades CD11b‐mediated fungal recognition by coating itself with capsular polysaccharides

Abstract

Cryptococcus gattii is a capsular pathogenic fungus causing life-threatening cryptococcosis.Although the capsular polysaccharides (CPs) of C. gattii are considered as virulence factors, the physiological significance of CP biosynthesis and of CPs themselves is not fully understood, with many conflicting data reported. First, we demonstrated that CAP gene deletant of C. gattii completely lacked capsule layer and its virulence, and that the strain was susceptible to host-related factors including oxidizing, hypoxic, and hypotrophic conditions in vitro. Extracellular CPs recovered from culture supernatant bound specifically to C. gattii acapsular strains, not to other fungi and immune cells, and rendered them the immune escape effects. In fact, dendritic cells (DCs) did not efficiently uptake the CP-treated acapsular strains, which possessed no visible capsule layer, and a decreased amount of phosphorylated proteins and cytokine levels after the stimulation. DCs recognized C. gattii acapuslar cells via an immune receptor CD11b-and Syk-related pathway; however, CD11b did not bind to CP-treated acapsular cells. These results suggested that CPs support immune evasion by coating antigens on C. gattii and blocking the interaction between CD11b and C. gattii cells. Here, we describe the importance of CPs in pathogenicity and immune evasion mechanisms of C. gattii.

Cryptococcus gattii polysaccharide capsule: An insight on fungal‐host interactions and vaccine studies

“…Ueno et al. [11] demonstrated that CP mediates the inhibition of the recognition of acapsular C. gattii by CD11b. The treatment of acapsular C. gattii with extracellular CP coated cell wall antigens.…”

“…In this issue of the European Journal of Immunology , Ueno et al. [11] provided new insights about the role of C. gattii CP by investigating mechanisms responsible for the low virulence of an acapsular C. gattii strain, which they previously described [12, 13]. They proved that C. gattii CP is essential for pathogenicity and evasion from the immune system.…”

“…The Ueno et al. [11] results demonstrate how the culture condition alters C. gattii structure and influences host–immune response. It also shows the importance of choosing different culture conditions when studying fungal pathogenicity.…”

“…In summary, Ueno et al. [11] provided new insights into the immunological effects of CP on C. gattii . The study demonstrates that CP can block the interaction between CD11b and C. gattii , affecting immune recognition.…”

Comparative miRNA Transcriptomics of Mouse and Macaque Reveals MYOC is An Inhibitor for C. neoformans Invasion into Brain

“…Occurrences of fungal invasive diseases are always caused by invading fungi and also involved with aspects of hosts closely [1][2][3]. Studies have shown the raised body temperature, limited nutrients of glucose and metal ions, phagocytosis by phagocytes and cellular immunities are powerful weapons for fungal elimination in hosts [4][5][6][7][8][9][10], while fungal evolved strategies in return, such as temperature resistance, polysaccharide capsule and melanin production, morphology switching, and virulence gene expressions [11][12][13][14][15][16]. Nonetheless, the mechanisms of fungal central nervous system (CNS) invasion have not been determined, which is also a mystery in cryptococcosis, a life-threatening fungal invasive disease, initialized by human pathogen Cryptococcus neoformans [17][18][19][20].…”