Sterilizing immunity in the lung relies on targeting fungal apoptosis-like programmed cell death
Open accessAbstract
Survivin' neutrophil surveillance: Humans constantly inhale fungal spores. Why don't we suffer more invasive infections from ubiquitous fungal molds such as Aspergillus fumigatus ? Working in mice, Shlezinger et al. found that neutrophils phagocytosed germinating fungal spores deep in the lungs (see the Perspective by Wiesner and Klein). Once engulfed, the fungal cells underwent programmed cell death, likely induced by phagocyte NADPH oxidase. Fungal strains engineered to overexpress a fungal survivin homolog resisted cell death by inhibiting caspase-3 and -7. When a Survivin antagonist was applied, more fungal cells died. These findings may lead to therapies for immunocompromised patients threatened by invasive fungal lung infections. Science , this issue p. 1037 ; see also p. 973
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Significant advances have been made in elucidating the main innate immune players and effector pathways for efficient control of Aspergillus infection in mouse models with the use of transgenic mice.
“Significant advances have been made in elucidating the main innate immune players and effector pathways for efficient control of Aspergillus infection in mouse models with the use of transgenic mice (189–202).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [189]
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- Authors
- Shlezinger, N., Irmer, H., Dhingra, S., Beattie, S. R., Cramer, R. A., Braus, G. H., Sharon, A., & Hohl, T. M.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- University of Göttingen (DE)
- Dartmouth College (US)
- Tel Aviv University (IL)
- Corresponding author
- Sharon, Amir
- Hohl, Tobias M.
- ORCID
- Venue
- Science
- Published
- 2017-09-08
- Volume
- 357
- Issue
- 6355
- Pages
- 1037-1041
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5628051
- OpenAlex
- W2753326298
- Cited by
- 105
- References
- 34
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 8 · 2023: 8 · 2022: 8 · 2021: 15 · 2020: 13 · 2019: 14 · 2018: 16 · 2017: 7
- FWCI
- 10.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (award303977, RO1 AI093808, award303979, R21 AI105617, award303984, T32-GM008704)
- Deutsche Forschungsgemeinschaft (award303983)
- Israel Science Foundation (award303982, 835/13)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- Aspergillus fumigatus, NADPH oxidase, caspase-3, caspase-7, immunocompromised patients, lung immunity
- MeSH terms
- Animals, Aspergillus fumigatus, Fungal Proteins, Immunologic Surveillance, Lung, Neutrophils, Nitrosamines, Spores, Fungal, Apoptosis, NADPH Oxidases, Myeloid Cells, Apoptosis Regulatory Proteins, Mice, Pulmonary Aspergillosis
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