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J Infect Dis DOI:10.1093/infdis/jiu290

Dectin-1-dependent LC3 recruitment to phagosomes enhances fungicidal activity in macrophages.

Publication TypeJournal Article
Year of Publication2014
AuthorsTam, JM, Mansour, MK, Khan, NS, Seward, M, Puranam, S, Tanne, A, Sokolovska, A, Becker, CE, Acharya, M, Baird, MA, Choi, AMK, Davidson, MW, Segal, BH, Lacy-Hulbert, A, Stuart, LM, Xavier, RJ, Vyas, JM
JournalJ Infect Dis
Date Published2014 Dec 01
KeywordsAnimals, beta-Glucans, Candida albicans, CARD Signaling Adaptor Proteins, Cell Line, Fungi, Interleukin-1beta, Interleukin-6, Intracellular Signaling Peptides and Proteins, Lectins, C-Type, Macrophages, Mice, Microtubule-Associated Proteins, Models, Biological, NADPH Oxidase, Phagosomes, Phosphorylation, Protein-Tyrosine Kinases, Reactive Oxygen Species, Signal Transduction, Syk Kinase, Tumor Necrosis Factor-alpha

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.


Alternate JournalJ. Infect. Dis.
PubMed ID24842831
PubMed Central IDPMC4271056
Grant ListP30 DK043351 / DK / NIDDK NIH HHS / United States
R01 AI079253 / AI / NIAID NIH HHS / United States
R01HL055330 / HL / NHLBI NIH HHS / United States
1R01AI092084 / AI / NIAID NIH HHS / United States
K08 AI110655 / AI / NIAID NIH HHS / United States
R01 AI097519 / AI / NIAID NIH HHS / United States
1R01AI097519 / AI / NIAID NIH HHS / United States
R01 GM102482 / GM / NIGMS NIH HHS / United States
R01 HL055330 / HL / NHLBI NIH HHS / United States
R01AI079253 / AI / NIAID NIH HHS / United States
R01 DK093695 / DK / NIDDK NIH HHS / United States
R01 AI092084 / AI / NIAID NIH HHS / United States