title: Beta-glucan is a fungal determinant for adhesion-dependent human neutrophil functions.
abstract: Candida albicans is a common cause of nosocomial infections whose virulence depends on the reversible switch from blastoconidia to hyphal forms. Neutrophils (or polymorphonuclear leukocytes (PMNs)) readily clear blastoconidia by phagocytosis, but filaments are too long to be ingested. Mechanisms regulating immune recognition and response to filamentous fungal pathogens are not well understood, although known risk factors for developing life-threatening infections are neutropenia or defects in the NADPH oxidase system. We show human PMNs generate a respiratory burst response to unopsonized hyphae. Ab specific for beta-glucan, a major component of yeast cell walls, blocks this response, establishing beta-glucan as a key molecular pattern recognized by PMNs in response to C. albicans. This study also elucidates recognition and signaling mechanisms used by PMNs in response to beta-glucan under conditions where phagocytosis cannot occur. Human PMNs adhered to immobilized beta-glucan and released an efficient plasma membrane respiratory burst. Ab blockade of the integrin complement receptor 3 (CD11b/CD18) significantly inhibited both of these functions. Furthermore, we show a role for p38 MAPK and actin but not protein kinase C zeta in generating the respiratory burst to beta-glucan. Taken together, results show that beta-glucan in C. albicans hyphae is accessible to PMNs and sufficient to support an innate immune response.
authors.affiliation: Department of Surgery, Division of Surgical Research, Rhode Island Hospital and Brown University School of Medicine, 593 Eddy Street, Providence, RI 02903, USA.
authors.forename: Liz M
authors.initials: LM
authors.lastname: Lavigne
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Albina
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Reichner
mesh_terms: D000199:Actins / Q000502:physiology; D002176:Candida albicans / Q000276:immunology*; D002448:Cell Adhesion; D002473:Cell Wall / Q000737:chemistry; D006801:Humans; D016177:Macrophage-1 Antigen / Q000502:physiology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D016897:Respiratory Burst / Q000276:immunology; D015398:Signal Transduction; D047071:beta-Glucans / Q000276:immunology* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D000199:Actins; D016177:Macrophage-1 Antigen; D047071:beta-Glucans; D048051:p38 Mitogen-Activated Protein Kinases