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Oxid Med Cell Longev. 2018 May 20;2018:4938649. doi: 10.1155/2018/4938649. eCollection 2018.

Phagocytosis of Candida albicans Inhibits Autophagic Flux in Macrophages.

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Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China.
Jiangsu Province Blood Center, Nanjing, Jiangsu 210042, China.
Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Suzhou Institute of Systems Medicine, Suzhou, Jiangsu 215123, China.


Autophagy machinery has roles in the defense against microorganisms such as Candida albicans. Lipidated LC3, the marker protein of autophagy, participates in the elimination of C. albicans by forming a single-membrane phagosome; this process is called LC3-associated phagocytosis (LAP). However, the influence of C. albicans on autophagic flux is not clear. In this study, we found that C. albicans inhibited LC3 turnover in macrophages. After the phagocytosis of C. albicans in macrophages, we observed fewer acridine orange-positive vacuoles and RFP-GFP-LC3 puncta without colocalization with phagocytized C. albicans. However, phagocytosis of C. albicans led to LC3 recruitment, but p62 and ATG9A did not colocalize with LC3 or C. albicans. These effects are due to an MTOR-independent pathway. Nevertheless, we found that the C. albicans pattern-associated molecular pattern β-glucan increased LC3 turnover. In addition, phagocytosis of C. albicans caused a decrease in BrdU incorporation. Blocking autophagic flux aggravated this effect. Our findings suggest that phagocytosis of C. albicans decreases autophagic flux but induces LAP in an MTOR-independent manner in macrophages. Occupation of LC3 by recruiting engulfed C. albicans might contribute to the inhibition of autophagic flux. Our study highlights the coordinated machinery between canonical autophagy and LAP that defends against C. albicans challenge.

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