AbstractHuman 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 (β‐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 β‐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 β‐glucan and GE2 inhibited phagocytosis and killing of Candida albicans by PMN (inhibition of killing was 54.8% for β‐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.