Neutrophil swarming delays the growth of clusters of pathogenic fungi

• Published in: Nature communications Vol. 11; no. 1; pp. 2031 - 15
• Main Authors: Hopke, Alex, Scherer, Allison, Kreuzburg, Samantha, Abers, Michael S., Zerbe, Christa S., Dinauer, Mary C., Mansour, Michael K., Irimia, Daniel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.04.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13/62; 14/34; 14/63; 142/126; 49/62; 631/250/2504; 631/250/255; 631/326/193/2544; Candida; Candida albicans - growth & development; Candidiasis - microbiology; Cell Line; Chronic granulomatous disease; Clusters; Colony-stimulating factor; CRISPR-Cas Systems; Enzymes; Extracellular Traps - metabolism; Fungi; Germination; Granulocyte Colony-Stimulating Factor - pharmacology; Granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Granulomatous Disease, Chronic - microbiology; Humanities and Social Sciences; Humans; Image Processing, Computer-Assisted; Leukocytes (granulocytic); Leukocytes (neutrophilic); Microarray Analysis; multidisciplinary; NAD(P)H oxidase; NADPH Oxidases - metabolism; Neutrophils; Neutrophils - cytology; Neutrophils - microbiology; Oxidase; Peroxidase; Peroxidase - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Science; Science (multidisciplinary); Swarming
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15834-4

Neutrophils employ several mechanisms to restrict fungi, including the action of enzymes such as myeloperoxidase (MPO) or NADPH oxidase, and the release of neutrophil extracellular traps (NETs). Moreover, they cooperate, forming “swarms” to attack fungi that are larger than individual neutrophils. Here, we designed an assay for studying how these mechanisms work together and contribute to neutrophil's ability to contain clusters of live Candida . We find that neutrophil swarming over Candida clusters delays germination through the action of MPO and NADPH oxidase, and restricts fungal growth through NET release within the swarm. In comparison with neutrophils from healthy subjects, those from patients with chronic granulomatous disease produce larger swarms against Candida , but their release of NETs is delayed, resulting in impaired control of fungal growth. We also show that granulocyte colony-stimulating factors (GCSF and GM-CSF) enhance swarming and neutrophil ability to restrict fungal growth, even during treatment with chemical inhibitors that disrupt neutrophil function. Neutrophils employ several mechanisms to control the growth of fungi, including enzymes, reactive oxygen species, extracellular traps, and formation of “swarms”. Here, Hopke et al. study how the different mechanisms work together, using an in vitro assay with human neutrophils and clusters of live Candida cells.