TY - JOUR
T1 - Neutrophil swarming delays the growth of clusters of pathogenic fungi
AU - Alex, Hopke
AU - Scherer, Allison
AU - Kreuzburg, Samantha
AU - Abers, Michael S.
AU - Zerbe, Christa S.
AU - Dinauer, Mary C.
AU - Mansour, Michael K.
AU - Irimia, Daniel
N1 - Funding Information:
This work was supported by grants from the National Institute of General Medical Sciences (GM092804) and the Shriners Hospitals for Children to D.I., National Institute of Allergy and Infectious Diseases (AI132638) to M.M., and National Heart, Lung, and Blood Institute (HL140837) and the Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital to M.C.D. M.A. and C.Z. were supported by the National Institute of Allergy and Infectious Diseases. A.H. is the recipient of a postdoctoral fellowship from Shriners Hospitals for Children. Microfabrication was conducted at the BioMEMS Research Center, supported by a grant from the National Institute of Biomedical Imaging and Bioengineering (EB002503).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85084005905&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-15834-4
DO - 10.1038/s41467-020-15834-4
M3 - Article
C2 - 32341348
AN - SCOPUS:85084005905
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2031
ER -