Dectin-1-triggered Recruitment of Light Chain 3 Protein to Phagosomes Facilitates Major Histocompatibility Complex Class II Presentation of Fungal-derived Antigens
Open accessAbstract
Dectin-1 is a pattern recognition receptor that is important for innate immune responses against fungi in humans and mice. Dectin-1 binds to β-glucans in fungal cell walls and triggers phagocytosis, production of reactive oxygen by the NADPH oxidase, and inflammatory cytokine production which all contribute to host immune responses against fungi. Although the autophagy pathway was originally characterized for its role in the formation of double-membrane compartments engulfing cytosolic organelles and debris, recent studies have suggested that components of the autophagy pathway may also participate in traditional phagocytosis. In this study, we show that Dectin-1 signaling in macrophages and bone marrow-derived dendritic cells triggers formation of LC3II, a major component of the autophagy machinery. Further, Dectin-1 directs the recruitment of LC3II to phagosomes, and this requires Syk, activation of reactive oxygen production by the NADPH oxidase, and ATG5. Using LC3-deficient dendritic cells we show that whereas LC3 recruitment to phagosomes is not important for triggering phagocytosis, killing or Dectin-1-mediated inflammatory cytokine production, it facilitates recruitment of MHC class II molecules to phagosomes and promotes presentation of fungal-derived antigens to CD4 T cells.
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The role of LAP in immunity against Aspergillus has not been shown for other fungi.
“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 [256]
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- Authors
- Ma, J., Becker, C., Lowell, C. A., & Underhill, D. M.
- Affiliations
- Cedars-Sinai Medical Center (US)
- University of California, San Francisco (US)
- Corresponding author
- Underhill, David M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 287
- Issue
- 41
- Pages
- 34149-34156
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3464523
- OpenAlex
- W1993648746
- Cited by
- 198
- References
- 26
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 4 · 2023: 13 · 2022: 8 · 2021: 14 · 2020: 15 · 2019: 14 · 2018: 20 · 2017: 20 · 2016: 28 · 2015: 16 · 2014: 20 · 2013: 16
- FWCI
- 12.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM-085796, R01GM085796)
- National Institute of Allergy and Infectious Diseases (R01AI068150, AI071116, R01AI065495, R01AI071116)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- Dectin-1, LC3-II, autophagy, phagosome, MHC class II presentation, fungal antigens, macrophages, dendritic cells, Syk, NADPH oxidase, reactive oxygen species, ATG5, β-glucan, CD4+ T cells, antigen presentation
- MeSH terms
- Autophagy-Related Protein 5, Syk Kinase, Dectin-1, Animals, Antigens, Fungal, Histocompatibility Antigens Class II, Bone Marrow Cells, Cell Line, Dendritic Cells, Enzyme Activation, Macrophages, Microtubule-Associated Proteins, Phagosomes, Protein Binding, Protein-Tyrosine Kinases, CD4-Positive T-Lymphocytes, Antigen Presentation, Mice, Knockout, NADPH Oxidases, Lectins, C-Type, beta-Glucans, Intracellular Signaling Peptides and Proteins, Mice
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