AUTHOR=Liu Wen-Na , Jiang Xiao-Yong , Xu Yan-Zhu , Sun Xiao-Han , Wu Kai-Xuan , Hu Xin-Lin , Lin Yong , Lin Li-Rong , Tong Man-Li , Liu Li-Li 

TITLE=Treponemapallidum Dysregulates Monocytes and Promotes the Expression of IL-1β and Migration in Monocytes Through the mTOR Signaling Pathway

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.592864

DOI=10.3389/fcimb.2020.592864

ISSN=2235-2988

ABSTRACT=<p>Monocytes are widely involved in the body’s defense response, and abnormally regulated monocyte subsets are closely related to the pathogenesis of various diseases. It is unclear whether <italic>Treponema pallidum</italic> (<italic>Tp</italic>) dysregulates monocyte subsets and impacts the functions of monocytes. This study aims to analyze the distribution of monocyte subsets in syphilis patients and the effect of <italic>Tp</italic> on monocyte functions to explore the pathogenesis of syphilis. Flow cytometry was employed to detect monocyte subsets. With or without pre-treatment with rapamycin, THP-1 cell migration stimulated by <italic>Tp</italic> was investigated by a Transwell migration assay, and THP-1 cell phagocytosis was studied using fluorescent microspheres. IL-1β and TNF-α expression was quantified by PCR and flow cytometry, while LC3 and mTOR were investigated in <italic>Tp</italic>-exposed THP-1 cells using western blotting. <italic>Tp</italic> infection led to an increase in the proportion of CD14<sup>++</sup>CD16<sup>+</sup> monocytes and a decrease in the proportion of CD14<sup>++</sup>CD16<sup>-</sup> monocytes. In addition, <italic>Tp</italic> promoted monocyte (THP-1) CD14 and CD16 expression <italic>in vitro</italic>, induced the expression of IL-1β and TNF-α in a dose-dependent manner and promoted the migration and autophagy of monocytes. Furthermore, mTOR phosphorylation on monocytes was stimulated by <italic>Tp</italic>, and the levels peaked at 30 min. Pre-treatment with rapamycin (mTOR inhibitor) attenuated the expression of IL-1β and migration in <italic>Tp</italic>-exposed THP-1 cells. <italic>Tp</italic> abnormally regulates monocyte subsets and promotes migration, autophagy, and the expression of IL-1β and TNF-α in THP-1 cells. Meanwhile, the mTOR affected the expression of IL-1β and migration in <italic>Tp</italic>-exposed THP-1 cells. This study is important as it sheds light on the mechanism by which monocytes interact with <italic>Tp</italic> during infection.</p>