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NLRP3 and mTOR Reciprocally Regulate Macrophage Phagolysosome Formation and Acidification Against Vibrio vulnificus Infection.


ABSTRACT: 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.

SUBMITTER: Huang XH 

PROVIDER: S-EPMC7578225 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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NLRP3 and mTOR Reciprocally Regulate Macrophage Phagolysosome Formation and Acidification Against <i>Vibrio vulnificus</i> Infection.

Huang Xian-Hui XH   Ma Yao Y   Zheng Meng-Meng MM   Chen Na N   Hu Mei-Na MN   Wu Liu-Ying LY   Zheng Yi Y   Lou Yong-Liang YL   Xie Dan-Li DL  

Frontiers in cell and developmental biology 20201008


The marine bacterium <i>Vibrio vulnificus</i> 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 <i>V. vulnificus</i> affects macrophages after phagocytosis is unclear. In this report, we found that the bactericidal activity of macrophages to internalize <i>V. vulnificus</i> was dependent on mammalian target of r  ...[more]

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