Pseudomonas aeruginosa promotes autophagy to suppress macrophage-mediated bacterial eradication

Wenting Qu; Yongjian Wu; Dandan Li; Yi Wang; Minhao Wu

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Pseudomonas aeruginosa promotes autophagy to suppress macrophage-mediated bacterial eradication

Wenting Qu 1,Yongjian Wu 1,Dandan Li 2,Yi Wang 1,Minhao Wu 1 * #

1.Department of Immunology, Institute of Tuberculosis Control, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China

2.Department of Clinical Laboratory, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 243000, China.

*Correspondence author

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Funding: 高等学校博士学科点专项科研基金新教师类资助课题（No.20120171120064）

Opened online: 2 June 2016

Accepted by: none

Citation: Wenting Qu,Yongjian Wu,Dandan Li.Pseudomonas aeruginosa promotes autophagy to suppress macrophage-mediated bacterial eradication[OL]. [ 2 June 2016] http://en.paper.edu.cn/en_releasepaper/content/4692951

Objectives: To explore the role of autophagy on macrophage-mediated phagocytosis and intracellular killing of Pseudomonas aeruginosa (PA), a common extracellular bacterium which often causes various opportunistic infections. Methods: Macrophages were infected with PA or stimulated with zymosan bioparticles. Autophagy was tested by fluorescent microscopy and Western blot for LC3. Phagocytosis and killing efficiency were assessed by plate count assay, flow cytometry or immunofluorescent staining. Phagocytic receptor expression, ROS generation and NO production were examined by PCR, flow cytometry and Griess reaction, respectively. Results: PA infection induced autophagy activation in both mouse and human macrophages. Induction of autophagy by rapamycin or starvation significantly inhibited PA internalization by downregulating phagocytosis receptor expression, and suppressed intracellular killing of PA via reducing ROS and NO production in macrophages. While knockdown of autophagy molecules ATG7 or Beclin1 enhanced macrophage-mediated phagocytosis and intracellular killing of PA. Conclusions: Our study suggested that PA promotes autophagy to suppress macrophage-mediated bacterial phagocytosis and intracellular killing. These insights demonstrated a novel immune evasion mechanism employed by PA, which may provide potential therapeutic strategies of PA infectious diseases.

Keywords:autophagy; phagocytosis; bacterial killing; macrophages; Pseudomonas aeruginosa

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