Neutrophils sense microbial size and selectively release neutrophil extracellular traps in response to large pathogens

Neutrophils are critical for antifungal defense, but the mechanisms that clear hyphae and other pathogens that are too large to be phagocytosed remain unknown. We show that neutrophils sense microbial size and selectively release neutrophil extracellular traps (NETs) in response to large pathogens, such as Candida albicans hyphae and extracellular Mycobacterium bovis aggregates, but not small yeast and single bacteria. NETs are fundamental in countering large pathogens in vivo. Phagocytosis via dectin-1, acts as a sensor for microbial size preventing NETosis by downregulating neutrophil elastase (NE) translocation to the nucleus. Dectin-1 deficiency leads to aberrant NETosis and NET-mediated tissue damage during infection. Size-tailored neutrophil responses clear large microbes and minimize pathology when microbes are small enough to be phagocytosed.