Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms

TLDR

Neutrophils eliminate microbes via phagocytosis, and Candida albicans—the leading fungal pathogen in humans—can switch between budding yeast and filamentous hyphae, a key virulence trait. Activated neutrophils release extracellular traps composed of granule proteins and chromatin that degrade virulence factors and kill bacteria; this study shows Candida albicans induces NET formation and is killed by NETs in both yeast and hyphal forms, with granule components mediating the killing.

Abstract

Neutrophils phagocytose and kill microbes upon phagolysosomal fusion. Recently we found that activated neutrophils form extracellular fibres that consist of granule proteins and chromatin. These neutrophil extracellular traps (NETs) degrade virulence factors and kill Gram positive and negative bacteria. Here we show for the first time that Candida albicans, a eukaryotic pathogen, induces NET-formation and is susceptible to NET-mediated killing. C. albicans is the predominant aetiologic agent of fungal infections in humans, particularly in immunocompromised hosts. One major virulence trait of C. albicans is its ability to reversibly switch from singular budding cells to filamentous hyphae. We demonstrate that NETs kill both yeast-form and hyphal cells, and that granule components mediate fungal killing. Taken together our data indicate that neutrophils trap and kill ascomycetous yeasts by forming NETs.