关键词: Cryptococcus gattii capsular polysaccharides dendritic cells fungal recognition integrins

Mesh : Animals CD11b Antigen / immunology Cryptococcosis / immunology Cryptococcus gattii / genetics immunology pathogenicity Cytokines / biosynthesis Dendritic Cells / immunology Female Fungal Capsules / genetics immunology Fungal Polysaccharides / genetics immunology Gene Deletion Humans Immune Evasion / immunology Mice Mice, Inbred C57BL Polysaccharides / genetics immunology Syk Kinase / metabolism Virulence Factors / immunology

来  源:   DOI:10.1002/eji.202049042   PDF(Sci-hub)

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.
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