Mechanisms involved in the triggering of neutrophil extracellular traps (NETs) by Candida glabrata during planktonic and biofilm growth
Open accessAbstract
Candida spp. adhere to medical devices, such as catheters, forming drug-tolerant biofilms that resist killing by the immune system. Little is known about how C. glabrata, an emerging pathogen, resists attack by phagocytes. Here we show that upon encounter with planktonic (non-biofilm) C. glabrata, human neutrophils initially phagocytose the yeast and subsequently release neutrophil extracellular traps (NETs), complexes of DNA, histones, and proteins capable of inhibiting fungal growth and dissemination. When exposed to C. glabrata biofilms, neutrophils also release NETs, but significantly fewer than in response to planktonic cells. Impaired killing of biofilm parallels the decrease in NET production. Compared to biofilm, neutrophils generate higher levels of reactive oxygen species (ROS) when presented with planktonic organisms, and pharmacologic inhibition of NADPH-oxidase partially impairs NET production. In contrast, inhibition of phagocytosis nearly completely blocks NET release to both biofilm and planktonic organisms. Imaging of the host response to C. glabrata in a rat vascular model of infection supports a role for NET release in vivo. Taken together, these findings show that C. glabrata triggers NET release. The diminished NET response to C. glabrata biofilms likely contributes to the resilience of these structured communities to host defenses.
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Human neutrophils release neutrophil extracellular traps after engulfment of C. glabrata cells.
“Human neutrophils have been reported to release neutrophil extracellular traps after engulfment of C. glabrata cells [141].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [141]
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- Authors
- Johnson, C. J., Kernien, J. F., Hoyer, A. R., & Nett, J. E.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Nett, Jeniel E.
- Venue
- Scientific Reports
- Published
- 2017-10-12
- Volume
- 7
- Issue
- 1
- Pages
- 13065-13065
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5638821
- OpenAlex
- W2763228608
- Cited by
- 58
- References
- 64
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 5 · 2022: 8 · 2021: 8 · 2020: 12 · 2019: 7 · 2018: 9
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Burroughs Wellcome Fund (K08 AI108727, 1012299)
- National Institutes of Health (1012299)
- National Institute of Allergy and Infectious Diseases (K08AI108727)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- neutrophil extracellular traps, Candida glabrata, fungal biofilms, neutrophil phagocytosis, reactive oxygen species, NADPH oxidase, host defense against fungi, catheter-related infection, antifungal immunity
- MeSH terms
- Animals, Cells, Cultured, Humans, Microscopy, Electron, Scanning, Neutrophils, Plankton, Reactive Oxygen Species, Biofilms, Candida glabrata, Rats, Extracellular Traps
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