%0 Journal Article
%T Quercetin induces itaconic acid-mediated M1/M2 alveolar macrophages polarization in respiratory syncytial virus infection.
%A An L
%A Zhai Q
%A Tao K
%A Xiong Y
%A Ou W
%A Yu Z
%A Yang X
%A Ji J
%A Lu M
%J Phytomedicine
%V 130
%N 0
%D 2024 Jul 25
%M 38797031
%F 6.656
%R 10.1016/j.phymed.2024.155761
%X <B>BACKGROUND: </B>Quercetin has received extensive attention for its therapeutic potential treating respiratory syncytial virus (RSV) infection diseases. Recent studies have highlighted quercetin's ability of suppressing alveolar macrophages (AMs)-derived lung inflammation. However, the anti-inflammatory mechanism of quercetin against RSV infection still remains elusive.<BR><B>OBJECTIVE: </B>This study aims to elucidate the mechanism about quercetin anti-inflammatory effect on RSV infection.<BR><B>METHODS: </B>BALB/c mice were intranasally infected with RSV and received quercetin (30, 60, 120 mg/kg/d) orally for 3 days. Additionally, an in vitro infection model utilizing mouse alveolar macrophages (MH-S cells) was employed to validate the proposed mechanism.<BR><B>RESULTS: </B>Quercetin exhibited a downregulatory effect on glycolysis and tricarboxylic acid (TCA) cycle metabolism in RSV-infected AMs. However, it increased itaconic acid production, a metabolite derived from citrate through activating immune responsive gene 1 (IRG1), and further inhibiting succinate dehydrogenase (SDH) activity. While the suppression of SDH activity orchestrated a cascading downregulation of Hif-1α/NLRP3 signaling, ultimately causing AMs polarization from M1 to M2 phenotypes.<BR><B>CONCLUSIONS: </B>Our study demonstrated quercetin stimulated IRG1-mediated itaconic acid anabolism and further inhibited SDH/Hif-1α/NLRP3 signaling pathway, which led to M1 to M2 polarization of AMs so as to ameliorate RSV-induced lung inflammation.