title: Phagocytosis by human neutrophils is stimulated by a unique fungal cell wall component.
abstract: Innate immunity depends upon recognition of surface features common to broad groups of pathogens. The glucose polymer beta-glucan has been implicated in fungal immune recognition. Fungal walls have two kinds of beta-glucan: beta-1,3-glucan and beta-1,6-glucan. Predominance of beta-1,3-glucan has led to the presumption that it is the key immunological determinant for neutrophils. Examining various beta-glucans for their ability to stimulate human neutrophils, we find that the minor cell wall component beta-1,6-glucan mediates neutrophil activity more efficiently than beta-1,3-glucan, as measured by engulfment, production of reactive oxygen species, and expression of heat shock proteins. Neutrophils rapidly ingest beads coated with beta-1,6-glucan while ignoring those coated with beta-1,3-glucan. Complement factors C3b/C3d are deposited on beta-1,6-glucan more readily than on beta-1,3-glucan. Beta-1,6-glucan is also important for efficient engulfment of the human pathogen Candida albicans. These unique stimulatory effects offer potential for directed stimulation of neutrophils in a therapeutic context.
authors.affiliation: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Ifat
authors.initials: I
authors.lastname: Rubin-Bejerano
authors.forename: Claudia
authors.initials: C
authors.lastname: Abeijon
authors.forename: Paula
authors.initials: P
authors.lastname: Magnelli
authors.forename: Paula
authors.initials: P
authors.lastname: Grisafi
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Fink
mesh_terms: D002175:Candida / Q000502:physiology*; D002473:Cell Wall / Q000502:physiology*; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D009504:Neutrophils / Q000382:microbiology / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000502:physiology*; D016133:Polymerase Chain Reaction; D047071:beta-Glucans / Q000494:pharmacology
chemical_list: D006360:Heat-Shock Proteins; D047071:beta-Glucans