Autophagy plays an essential role in the clearance of Pseudomonas aeruginosa by alveolar macrophages

Author:

Yuan Kefei12,Huang Canhua1,Fox John2,Laturnus Donna3,Carlson Edward3,Zhang Binjie1,Yin Qi1,Gao Hongwei4,Wu Min2

Affiliation:

1. The State Key Laboratory for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China

2. Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, ND 58203-9037, USA

3. Department of Anatomy and Cell Biology, University of North Dakota, Grand Forks, ND 58203-9037, USA

4. Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

Abstract

Intracellular bacteria have been shown to cause autophagy, which impacts infectious outcomes, whereas extracellular bacteria have not been reported to activate autophagy. Here, we demonstrate that Pseudomonas aeruginosa, a Gram-negative extracellular bacterium, activates autophagy with considerably increased LC3 punctation in both an alveolar macrophage cell line (MH-S) and primary alveolar macrophages. Using the LC3 Gly120 mutant, we successfully demonstrated a hallmark of autophagy, conjugation of LC3 to phosphatidylethanolamine (PE). The accumulation of typical autophagosomes with double membranes was identified morphologically by transmission electron microscopy (TEM). Furthermore, the increase of PE-conjugated LC3 was indeed induced by infection rather than inhibition of lysosome degradation. P. aeruginosa induced autophagy through the classical beclin-1–Atg7–Atg5 pathway as determined by specific siRNA analysis. Rapamycin and IFN-γ (autophagy inducers) augmented bacterial clearance, whereas beclin-1 and Atg5 knockdown reduced intracellular bacteria. Thus, P. aeruginosa-induced autophagy represents a host protective mechanism, providing new insight into the pathogenesis of this infection.

Publisher

The Company of Biologists

Subject

Cell Biology

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