1723. Dectin-1 mediated LC3 recruitment to phagosomes promotes fungal killing in macrophages
Session: Poster Abstract Session: Studies of the Interface of Host-Microbial Interaction
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Background: A role for autophagy in phagocytosis and host defense against fungal pathogens has been postulated, though the molecular details remain unclear.  Reversible conjugation of LC3 to the autophagosomal membrane is a hallmark of autophagy.

Methods: We used live cell imaging coupled with biochemistry to evaluate the role of Dectin-1 on LC3 recruitment to the fungal phagosome.

Results: We show that LC3-deficient primary macrophages demonstrate diminished fungicidal activity, but increased cytokine production in response to Candida albicans. To evaluate the molecular mechanism governing regulation of LC3 onto phagosomes, we observed that LC3 is recruited to fungal phagosomes through activation of Dectin-1. LC3 recruitment to the phagosome requires Syk-dependent phosphorylation of Dectin-1, but is independent of signaling through Toll-like receptors (TLRs) and does not require the presence of Card9. We further demonstrate that ROS generation by NADPH oxidase is required for LC3 recruitment to the fungal phagosome.

Conclusion: These observations directly link LC3 to host defense and inflammatory pathway in macrophages against C. albicans.

Jenny Tam, Ph.D.1, Michael Mansour, M.D., Ph.D.2, Nida Khan, B.S.1 and Jatin M. Vyas, M.D., Ph.D.3, (1)Massachsetts General Hospital, Division of Infectious Diseases, Boston, MA, (2)Massachusetts General Hospital, Division of Infectious Diseases, Boston, MA, (3)Massachusetts General Hospital, Division of Infectious Disease, Boston, MA

Disclosures:

J. Tam, None

M. Mansour, None

N. Khan, None

J. M. Vyas, None

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