AUTHOR=Dong Kai , Jiang Ziyang , Zhang Jianhui , Qin Hanxiao , Chen Jianping , Chen Qiwei 

TITLE=The role of SIRT1 in the process of Toxoplasma gondii infection of RAW 264.7 macrophages

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1017696

DOI=10.3389/fmicb.2022.1017696

ISSN=1664-302X

ABSTRACT=<p><italic>Toxoplasma gondii</italic> is an opportunistic pathogenic protozoan that can infect almost all kinds of warm-blooded animals, including humans. <italic>T. gondii</italic> can evade the host's immune response, a process known as immune evasion. Our main objective was to evaluate the role played by Sirtuin1 (SIRT1) [one of the sirtuins (SIRTs) that are a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases (HDACs)] in the <italic>T. gondii</italic> infection of RAW264.7 macrophages. In this study, we evaluated and observed alterations in the activity, expression, and localization of SIRT1 and assessed its involvement in the CD154/IFN-γ (CD40 ligand/interferon gamma) killing pathway and in autophagy during <italic>T. gondii</italic> infection. The inhibition of SIRT1 in host cells effectively reduced the number of intracellular tachyzoites, and the mechanism behind this effect might be the upregulation of IRGM1 [murine ortholog of IRGM (immunity-related GTPase family M)] and the initiation of autophagy. To the best of our knowledge, our study is the first to prove that <italic>T. gondii</italic> infection upregulates SIRT1 in RAW264.7 cells and that the inhibition of SIRT1 reduces the number of intracellular tachyzoites. Moreover, the upregulation of IRGM1 and the activation of autophagy may contribute to the intracellular inhibition of <italic>T. gondii</italic> caused by SIRT1 inhibition.</p>