AUTHOR=Huang Xian-Hui , Ma Yao , Lou Han , Chen Na , Zhang Ting , Wu Liu-Ying , Chen Yi-Ju , Zheng Meng-Meng , Lou Yong-Liang , Xie Dan-Li 

TITLE=The Role of TSC1 in the Macrophages Against Vibrio vulnificus Infection

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.596609

DOI=10.3389/fcimb.2020.596609

ISSN=2235-2988

ABSTRACT=<p><italic>Vibrio vulnificus</italic> (<italic>V. vulnificus</italic>) is an estuarine bacterium that is capable of causing rapidly fatal infection in humans. Proper polarization and bactericidal activity of macrophages play essential roles in defending against invading pathogens. How macrophages limit <italic>V. vulnificus</italic> infection remains not well understood. Here we report that tuberous sclerosis complex 1 (TSC1) is crucial for the regulation of <italic>V. vulnificus</italic>-induced macrophage polarization, bacterial clearance, and cell death. Mice with myeloid-specific deletion of TSC1 exhibit a significant reduction of survival time after <italic>V. vulnificus</italic> infection. <italic>V. vulnificus</italic> infection induces both M1 and M2 polarization. However, TSC1 deficient macrophages show enhanced M1 response to <italic>V. vulnificus</italic> infection. Interestedly, the absence of TSC1 in myeloid cells results in impaired bacterial clearance both <italic>in vivo</italic> and <italic>in vitro</italic> after <italic>V. vulnificus</italic> infection. Inhibition of the mammalian target of rapamycin (mTOR) activity significantly reverses <italic>V. vulnificus</italic>-induced hypersensitive M1 response and resistant bactericidal activity both in wild-type and TSC1-deficient macrophages. Moreover, <italic>V. vulnificus</italic> infection causes cell death of macrophages, possibly contributes to defective of bacterial clearance, which also exhibits in a mTORC1-dependent manner. These findings highlight an essential role for the TSC1-mTOR signaling in the regulation of innate immunity against <italic>V. vulnificus</italic> infection.</p>