The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
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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Cites
Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem
Pfaller, M. A., & Diekema, D. J. (2007) · Clinical Microbiology Reviews · doi:10.1128/cmr.00029-06 · Cited by 4,174 · cited 1×
“Invasive candidiasis is a leading cause of death among immunocompromised patients and has a crude mortality rate of >50% [1].”
BackgroundGuidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996 · cited 1×
“The degree of endogenous lipidated LC3 (LC3-II) correlates with the fraction of LC3 inserted onto phagosomal or autophagosomal membranes [26].”
Autophagy in immunity and inflammation
Levine, B., Mizushima, N., & Virgin, H. W. (2011) · Nature · doi:10.1038/nature09782 · Cited by 3,289
Nakahira, K., Haspel, J. A., Rathinam, V. A. K., Lee, S.-J., Dolinay, T., Lam, H. C., Englert, J. A., Rabinovitch, M., Cernadas, M., Kim, H. P., et al. (2011) · Nature Immunology · doi:10.1038/ni.1980 · Cited by 3,049
Self-citationHow to Interpret LC3 Immunoblotting
Mizushima, N., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4600 · Cited by 2,595 · cited 1×
“Densitometry was used to quantitate the total amount of LC3-II produced [28], confirming that dectin-1 macrophages produce a greater amount of LC3-II than dectin-1 macrophages (Figure 3C and 3E ) when stimulated with both heat-killed C.”
MethodKimura, S., Noda, T., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4451 · Cited by 2,278
Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4
Scherz‐Shouval, R., Shvets, E., Fass, E., Shorer, H., Gil, L., & Elazar, Z. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601623 · Cited by 2,101 · cited 1×
“tion-induced autophagy, as the LC3 lipidation factor Atg4 is regulated by ROS [40, 41] The role of ROS in LC3 lipidation was also examined in LC3β and beclin-1 (another autophagy-related protein) macrophages, whereby NALP3 inflammasome activation by lipopolysaccharide (LPS) and adenosine triphosphate produced more ROS.”
BackgroundNonfilamentous C. albicans Mutants Are Avirulent
Lo, H.-J., Köhler, J. R., DiDomenico, B., Loebenberg, D., Cacciapuoti, A., & Fink, G. R. (1997) · Cell · doi:10.1016/s0092-8674(00)80358-x · Cited by 1,809
Rioux, J. D., Xavier, R. J., Taylor, K. D., Silverberg, M. S., Goyette, P., Huett, A., Green, T., Kuballa, P., Barmada, M. M., Datta, L. W., et al. (2007) · Nature Genetics · doi:10.1038/ng2032 · Cited by 1,769
Self-citationCollaborative Induction of Inflammatory Responses by Dectin-1 and Toll-like Receptor 2
Gantner, B. N., Simmons, R. M., Canavera, S. J., Akira, S., & Underhill, D. M. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021787 · Cited by 1,682
Cited by
Sorted by citations
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Self-citationAspergillus fumigatus and Aspergillosis in 2019
Latgé, J.-P., & Chamilos, G. (2019) · Clinical Microbiology Reviews · doi:10.1128/cmr.00140-18 · Cited by 1,400
Matsuzawa, Y., Hwang, S., & Cadwell, K. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053253 · Cited by 384
Modulation of inflammation by autophagy: Consequences for human disease
Netea-Maier, R. T., Plantinga, T. S., van de Veerdonk, F. L., Smit, J. W., & Netea, M. G. (2016) · Autophagy · doi:10.1080/15548627.2015.1071759 · Cited by 349
LC3-Associated Phagocytosis in Myeloid Cells Promotes Tumor Immune Tolerance
Cunha, L. D., Yang, M., Carter, R., Guy, C., Harris, L., Crawford, J. C., Quarato, G., Boada-Romero, E., Kalkavan, H., Johnson, M. D. L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.08.061 · Cited by 334
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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