PMID- 33117816 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201030 IS - 2296-634X (Print) IS - 2296-634X (Electronic) IS - 2296-634X (Linking) VI - 8 DP - 2020 TI - NLRP3 and mTOR Reciprocally Regulate Macrophage Phagolysosome Formation and Acidification Against Vibrio vulnificus Infection. PG - 587961 LID - 10.3389/fcell.2020.587961 [doi] LID - 587961 AB - The marine bacterium Vibrio vulnificus causes potentially fatal bloodstream infections, typically in patients with chronic liver diseases. The inflammatory response and anti-bacterial function of phagocytes are crucial for limiting bacterial infection in the human hosts. How V. vulnificus affects macrophages after phagocytosis is unclear. In this report, we found that the bactericidal activity of macrophages to internalize V. vulnificus was dependent on mammalian target of rapamycin (mTOR) and NOD-like receptor (NLR) family pyrin domain containing 3 (NLRP3) interaction. Additionally, the NLRP3 expression was dependent on mTORC1 activation. Inhibited mTORC1 or absence of NLRP3 in macrophages impaired V. vulnificus-induced phagosome acidification and phagolysosome formation, leading to a reduction of intracellular bacterial clearance. mTORC1 signaling overactivation could increase NLRP3 expression and restore insufficient phagosome acidification. Together, these findings indicate that the intracellular bactericidal activity of macrophages responding to V. vulnificus infection is tightly controlled by the crosstalk of NLRP3 and mTOR and provide critical insight into the host bactericidal activity basis of clearance of V. vulnificus through lyso/phagosome. CI - Copyright (c) 2020 Huang, Ma, Zheng, Chen, Hu, Wu, Zheng, Lou and Xie. FAU - Huang, Xian-Hui AU - Huang XH AD - Department of Microbiology and Immunology, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China. AD - Key Laboratory of Laboratory Medicine, Ministry of Education of China, Wenzhou, China. AD - Wenzhou Key Laboratory of Sanitary Microbiology, Wenzhou, China. FAU - Ma, Yao AU - Ma Y AD - Department of Microbiology and Immunology, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China. AD - Key Laboratory of Laboratory Medicine, Ministry of Education of China, Wenzhou, China. FAU - Zheng, Meng-Meng AU - Zheng MM AD - Department of Microbiology and Immunology, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China. AD - Key Laboratory of Laboratory Medicine, Ministry of Education of China, Wenzhou, China. FAU - Chen, Na AU - Chen N AD - Department of Microbiology and Immunology, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China. AD - Key Laboratory of Laboratory Medicine, Ministry of Education of China, Wenzhou, China. FAU - Hu, Mei-Na AU - Hu MN AD - Department of Microbiology and Immunology, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China. AD - Key Laboratory of Laboratory Medicine, Ministry of Education of China, Wenzhou, China. FAU - Wu, Liu-Ying AU - Wu LY AD - Department of Microbiology and Immunology, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China. AD - Key Laboratory of Laboratory Medicine, Ministry of Education of China, Wenzhou, China. FAU - Zheng, Yi AU - Zheng Y AD - Department of Microbiology and Immunology, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China. AD - Key Laboratory of Laboratory Medicine, Ministry of Education of China, Wenzhou, China. AD - Wenzhou Key Laboratory of Sanitary Microbiology, Wenzhou, China. FAU - Lou, Yong-Liang AU - Lou YL AD - Department of Microbiology and Immunology, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China. AD - Key Laboratory of Laboratory Medicine, Ministry of Education of China, Wenzhou, China. AD - Wenzhou Key Laboratory of Sanitary Microbiology, Wenzhou, China. FAU - Xie, Dan-Li AU - Xie DL AD - Department of Microbiology and Immunology, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China. AD - Key Laboratory of Laboratory Medicine, Ministry of Education of China, Wenzhou, China. AD - Wenzhou Key Laboratory of Sanitary Microbiology, Wenzhou, China. LA - eng PT - Journal Article DEP - 20201008 PL - Switzerland TA - Front Cell Dev Biol JT - Frontiers in cell and developmental biology JID - 101630250 PMC - PMC7578225 OTO - NOTNLM OT - NLRP3 OT - Vibrio vulnificus OT - acidification OT - bactericidal activity OT - mTOR OT - phagolysosome EDAT- 2020/10/30 06:00 MHDA- 2020/10/30 06:01 PMCR- 2020/01/01 CRDT- 2020/10/29 05:54 PHST- 2020/07/27 00:00 [received] PHST- 2020/09/07 00:00 [accepted] PHST- 2020/10/29 05:54 [entrez] PHST- 2020/10/30 06:00 [pubmed] PHST- 2020/10/30 06:01 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fcell.2020.587961 [doi] PST - epublish SO - Front Cell Dev Biol. 2020 Oct 8;8:587961. doi: 10.3389/fcell.2020.587961. eCollection 2020.