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Dectin-1–Dependent LC3 Recruitment to Phagosomes Enhances Fungicidal Activity in Macrophages
Open accessAbstract
Autophagy has been postulated to play role in mammalian host defense against fungal pathogens, although the molecular details remain unclear. Here, we show that primary macrophages deficient in the autophagic factor LC3 demonstrate diminished fungicidal activity but increased cytokine production in response to Candida albicans stimulation. LC3 recruitment to fungal phagosomes requires activation of the fungal pattern receptor dectin-1. LC3 recruitment to the phagosome also requires Syk signaling but is independent of all activity by Toll-like receptors and does not require the presence of the adaptor protein Card9. We further demonstrate that reactive oxygen species generation by NADPH oxidase is required for LC3 recruitment to the fungal phagosome. These observations directly link LC3 to the inflammatory pathway against C. albicans in macrophages.
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“Of interest, the role of LAP in immunity against Aspergillus (200, 245) has not been shown for other fungi (255–257).”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [255]
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Metadata
- Authors
- Tam, J. M., Mansour, M. K., Khan, N. S., Seward, M., Puranam, S., Tanne, A., Sokolovska, A., Becker, C. E., Acharya, M., Baird, M. A., Choi, A. M. K., Davidson, M. W., Segal, B. H., Lacy-Hulbert, A., Stuart, L. M., Xavier, R. J., & Vyas, J. M.
- Affiliations
- Harvard University (US)
- Tisch Cancer Institute (US)
- Massachusetts General Hospital (US)
- Broad Institute (US)
- Benaroya Research Institute (US)
- Florida State University (US)
- Weill Cornell Medicine (US)
- Roswell Park Comprehensive Cancer Center (US)
- Corresponding author
- Tam, Jenny M.
- ORCID
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-05-19
- Volume
- 210
- Issue
- 11
- Pages
- 1844-1854
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC4271056
- OpenAlex
- W2069844386
- Cited by
- 101
- References
- 48
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 9 · 2020: 10 · 2019: 14 · 2018: 12 · 2017: 9 · 2016: 12 · 2015: 6 · 2014: 1
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL055330)
- National Institute of Allergy and Infectious Diseases (R01AI092084, R01AI097519, R01AI079253)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- Dectin-1, LC3, autophagy, macrophages, Candida albicans, phagosome, fungal pathogen defense, Syk signaling, NADPH oxidase, reactive oxygen species, cytokine production, CARD9, Toll-like receptors
- MeSH terms
- Syk Kinase, Dectin-1, Animals, Candida albicans, Cell Line, Fungi, Macrophages, Microtubule-Associated Proteins, Models, Biological, Phagosomes, Phosphorylation, Protein-Tyrosine Kinases, Proteoglycans, Tumor Necrosis Factor-alpha, Signal Transduction, Interleukin-6, Reactive Oxygen Species, NADPH Oxidases, Lectins, C-Type, beta-Glucans, Intracellular Signaling Peptides and Proteins, Mice, CARD Signaling Adaptor Proteins, Interleukin-1beta
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