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

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

The Journal of infectious diseases (2014-05-21)
Jenny M Tam, Michael K Mansour, Nida S Khan, Michael Seward, Sravanthi Puranam, Antoine Tanne, Anna Sokolovska, Christine E Becker, Mridu Acharya, Michelle A Baird, Augustine M K Choi, Michael W Davidson, Brahm H Segal, Adam Lacy-Hulbert, Lynda M Stuart, Ramnik J Xavier, Jatin M Vyas
ABSTRACT

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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