title: Pseudomonas aeruginosa Triggers Macrophage Autophagy To Escape Intracellular Killing by Activation of the NLRP3 Inflammasome.
abstract: Assembly of the inflammasome has recently been identified to be a critical event in the initiation of inflammation. However, its role in bacterial killing remains unclear. Our study demonstrates that Pseudomonas aeruginosa infection induces the assembly of the NLRP3 inflammasome and the sequential secretion of caspase1 and interleukin-1β (IL-1β) in human macrophages. More importantly, activation of the NLRP3 inflammasome reduces the killing of P. aeruginosa in human macrophages, without affecting the generation of antimicrobial peptides, reactive oxygen species, and nitric oxide. In addition, our results demonstrate that P. aeruginosa infection increases the amount of the LC3-II protein and triggers the formation of autophagosomes in human macrophages. The P. aeruginosa-induced autophagy was enhanced by overexpression of NLRP3, ASC, or caspase1 but was reduced by knockdown of these core molecules of the NLRP3 inflammasome. Treatment with IL-1β enhanced autophagy in human macrophages. More importantly, IL-1β decreased the macrophage-mediated killing of P. aeruginosa, whereas knockdown of ATG7 or Beclin1 restored the IL-1β-mediated suppression of bacterial killing. Collectively, our study explores a novel mechanism employed by P. aeruginosa to escape from phagocyte killing and may provide a better understanding of the interaction between P. aeruginosa and host immune cells, including macrophages.
authors.affiliation: Department of Immunology, Zhongshan School of Medicine, Institute of Human Virology, Institute of Tuberculosis Control, Sun Yat-sen University, Guangzhou, China Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
authors.forename: Qiuchan
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Department of Immunology, Zhongshan School of Medicine, Institute of Human Virology, Institute of Tuberculosis Control, Sun Yat-sen University, Guangzhou, China Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Zhongshan School of Medicine, Institute of Human Virology, Institute of Tuberculosis Control, Sun Yat-sen University, Guangzhou, China Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Immunology, Zhongshan School of Medicine, Institute of Human Virology, Institute of Tuberculosis Control, Sun Yat-sen University, Guangzhou, China Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Immunology, Zhongshan School of Medicine, Institute of Human Virology, Institute of Tuberculosis Control, Sun Yat-sen University, Guangzhou, China Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Immunology, Zhongshan School of Medicine, Institute of Human Virology, Institute of Tuberculosis Control, Sun Yat-sen University, Guangzhou, China Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Immunology, Zhongshan School of Medicine, Institute of Human Virology, Institute of Tuberculosis Control, Sun Yat-sen University, Guangzhou, China Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
authors.forename: Jieying
authors.initials: J
authors.lastname: Pu
authors.affiliation: Department of Immunology, Zhongshan School of Medicine, Institute of Human Virology, Institute of Tuberculosis Control, Sun Yat-sen University, Guangzhou, China Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China wuminhao@mail.sysu.edu.cn.
authors.forename: Minhao
authors.initials: M
authors.lastname: Wu
mesh_terms: D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy / Q000276:immunology*; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D020170:Caspase 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010587:Phagocytosis / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C508585:IL1B protein, human; D053583:Interleukin-1beta; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C402202:PYCARD protein, human; D034741:RNA, Small Interfering; D020170:Caspase 1; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes