Dectin-1 promotes fungicidal activity of human neutrophils

Human polymorphonuclear leukocytes (PMN) are a first line of defense against Fungal infections. PMN express numerous Pattern Recognition Receptors (PRR) that facilitate identification of invading Microorganisms and ultimately promote resolution of disease. Dectin-1 (beta-glucan receptor) is a PRR expressed on several cell types and has been studied on monocytes and macrophages. However, the role played by Dectin-1 in the recognition and killing of fungi by PMN is unknown. We investigated the ability of Dectin-1 to mediate human PMN phagocytosis and fungicidal activity. Dectin-1 was expressed on the surface of PMN from all subjects tested (n=29) and in an intracellular compartment that co-sedimented with azurophilic granules in Percoll density gradients. Soluble beta-glucan and mAb GE2 (anti-dectin-1) inhibited binding and phagocytosis of zymosan by human PMN (e.g., ingestion was inhibited 40.1% by 30 min, p<0.001), and blocked Reactive Oxygen Species production. Notably, soluble beta-glucan and GE2 inhibited phagocytosis and killing of Candida albicans by PMN (inhibition of killing was 54.8% for beta-glucan and 36.2% for GE2, p<0.01). Our results reveal a mechanism whereby PMN Dectin-1 plays a key role in the recognition and killing of Fungal pathogens by the innate immune system.