Neutrophil swarming delays the growth of clusters of pathogenic fungi

Alex Hopke, Allison Scherer, Samantha Kreuzburg, Michael S. Abers, Christa S. Zerbe, Mary C. Dinauer, Michael K. Mansour and Daniel Irimia ()
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Alex Hopke: Massachusetts General Hospital
Allison Scherer: Harvard Medical School
Samantha Kreuzburg: National Institutes of Health (NIH)
Michael S. Abers: National Institutes of Health (NIH)
Christa S. Zerbe: National Institutes of Health (NIH)
Mary C. Dinauer: Washington University School of Medicine in St. Louis
Michael K. Mansour: Harvard Medical School
Daniel Irimia: Massachusetts General Hospital

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15834-4

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DOI: 10.1038/s41467-020-15834-4

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