Phagocytosis by Human Neutrophils Is Stimulated by a Unique Fungal Cell Wall Component

Phagocytosis by Human Neutrophils Is Stimulated by a Unique Fungal Cell Wall Component

SummaryInnate immunity depends upon recognition of surface features common to broad groups of pathogens. The glucose polymer β-glucan has been implicated in fungal immune recognition. Fungal walls have two kinds of β-glucan: β-1,3-glucan and β-1,6-glucan. Predominance of β-1,3-glucan has led to the presumption that it is the key immunological determinant for neutrophils. Examining various β-glucans for their ability to stimulate human neutrophils, we find that the minor cell wall component β-1,6-glucan mediates neutrophil activity more efficiently than β-1,3-glucan, as measured by engulfment, production of reactive oxygen species, and expression of heat shock proteins. Neutrophils rapidly ingest beads coated with β-1,6-glucan while ignoring those coated with β-1,3-glucan. Complement factors C3b/C3d are deposited on β-1,6-glucan more readily than on β-1,3-glucan. β-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. KeywordsMICROBIOCELLIMMUNO IntroductionThe cell walls of fungi evoke a powerful immunostimulatory response and have been proposed for use as potential anti-infective and antitumor drugs (Hong et al., 2003, 2004; Reynolds et al., 1980; Tzianabos et al., 1998). Both pathogenic (C