title: An alpha-glucan of Pseudallescheria boydii is involved in fungal phagocytosis and Toll-like receptor activation.
abstract: The host response to fungi is in part dependent on activation of evolutionarily conserved receptors, including toll-like receptors and phagocytic receptors. However, the molecular nature of fungal ligands responsible for this activation is largely unknown. Herein, we describe the isolation and structural characterization of an alpha-glucan from Pseudallescheria boydii cell wall and evaluate its role in the induction of innate immune response. These analyses indicate that alpha-glucan of P. boydii is a glycogen-like polysaccharide consisting of linear 4-linked alpha-D-Glcp residues substituted at position 6 with alpha-D-Glcp branches. Soluble alpha-glucan, but not beta-glucan, led to a dose-dependent inhibition of conidia phagocytosis. Furthermore, a significant decrease in the phagocytic index occurred when alpha-glucan from conidial surface was removed by enzymatic treatment with alpha-amyloglucosidase, thus indicating an essential role of alpha-glucan in P. boydii internalization by macrophages. alpha-Glucan stimulates the secretion of inflammatory cytokines by macrophages and dendritic cells; again this effect is abolished by treatment with alpha-amyloglucosidase. Finally, alpha-glucan induces cytokine secretion by cells of the innate immune system in a mechanism involving toll-like receptor 2, CD14, and MyD88. These results might have relevance in the context of infections with P. boydii and other fungi, and alpha-glucan could be a target for intervention during fungal infections.
authors.affiliation: Departamento de Microbiologia Geral and Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Vera Carolina B
authors.initials: VC
authors.lastname: Bittencourt
authors.forename: Rodrigo T
authors.initials: RT
authors.lastname: Figueiredo
authors.forename: Rosana B
authors.initials: RB
authors.lastname: da Silva
authors.forename: Diego S
authors.initials: DS
authors.lastname: Mourão-Sá
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Fernandez
authors.forename: Guilherme L
authors.initials: GL
authors.lastname: Sassaki
authors.forename: Barbara
authors.initials: B
authors.lastname: Mulloy
authors.forename: Marcelo T
authors.initials: MT
authors.lastname: Bozza
authors.forename: Eliana
authors.initials: E
authors.lastname: Barreto-Bergter
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D000818:Animals; D002240:Carbohydrate Sequence; D003713:Dendritic Cells / Q000166:cytology; D005936:Glucans / Q000737:chemistry*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88; D010587:Phagocytosis; D011541:Pseudallescheria / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005936:Glucans; D018950:Lipopolysaccharide Receptors; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors