title: The Cryptococcus neoformans cap10 and cap59 mutant strains, affected in glucuronoxylomannan synthesis, differentially activate human dendritic cells.
abstract: The human pathogen Cryptococcus neoformans causes meningo-encephalitis. The polysaccharide capsule is one of the main virulence factors and consists of two distinct polysaccharides: glucuronoxylomannan and galactoxylomannan. The presence of this polysaccharide capsule was previously shown to interfere with maturation of human dendritic cells (DCs), possibly by shielding cell-wall components from interacting with these host immune cells. Here we show that two mutant strains of C. neoformans, both lacking a visible capsule due to a defect in glucuronoxylomannan synthesis, differentially activate human monocyte-derived DCs. Cells from a cap59 mutant, but not of a cap10 mutant strain, induce maturation of DCs as indicated by an increase in the expression of the costimulatory molecules CD80 and CD86, and production of the cytokines interleukin (IL)-10, IL-12p40 and tumor necrosis factor alpha. Interestingly, cap59 mutant cells reassociated with a concentrated culture medium of wild-type C. neoformans had lost their capacity to induce DC maturation. Summarizing, our data suggest that glucuronoxylomannan confers properties to the capsule that protect the fungus against activation of DCs; however, the presence of intact glucuronoxylomannan is not an absolute requirement to prevent activation of DCs.
authors.affiliation: Department of Biology, Microbiology, Institute of Biomembranes, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Grijpstra
authors.forename: Boris
authors.initials: B
authors.lastname: Tefsen
authors.forename: Irma
authors.initials: I
authors.lastname: van Die
authors.forename: Hans
authors.initials: H
authors.lastname: de Cock
mesh_terms: D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003455:Cryptococcus neoformans / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D011134:Polysaccharides / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; C121601:CAP10 protein, Cryptococcus neoformans; C087781:CAP59 protein, Cryptococcus neoformans; C497964:CD86 protein, human; D017077:Culture Media, Conditioned; D016207:Cytokines; D005656:Fungal Proteins; D011134:Polysaccharides; C027478:glucuronoxylomannan