Myriocin enhances the clearance of M. tuberculosis by macrophages through the activation of PLIN2

Zhang, Ximeng1; Ding, Guanggui2; Yang, Xirui3; Lu, Hailin4; Xu, Yuzhong5; Hu, Yunlong1; Liu, Song2; Zhang, Huihua1; Huang, Kaisong6; Deng, Guofang7; Ye, Taosheng7; Yu, Qing1; Cai, Yi1; Xie, Shuixiang4; Wang, Wenfei7; Chen, Xinchun1,7

2024-06-01

10.1128/msphere.00257-24

MSPHERE   影响因子和分区

2379-5042

Myriocin is an inhibitor of de novo synthesis of sphingolipids and ceramides. In this research, we showed myriocin could significantly reduce Mtb burden and histopathological inflammation in mice. However, the underlying mechanism remains unclear. RNA-seq analysis revealed a significant increase in gene expression of PLIN2/CD36/CERT1 after myriocin treatment. The reduced bactericidal burden was only reversed after silencing the lipid droplets (LDs) surface protein PLIN2. This suggests that myriocin enhances the ability of macrophages to clear Mtb depending on the PLIN2 gene, which is part of the PPAR gamma pathway. Indeed, we observed a significant increase in the number of LDs following myriocin treatment. IMPORTANCE Mycobacterium tuberculosis has the ability to reprogram host cell lipid metabolism and alter the antimicrobial functions of infected macrophages. The sphingolipids, such as ceramides, are the primary host lipids utilized by the bacteria, making the sphingomyelinase/ceramide system critical in Mtb infections. Surprisingly, the antimicrobial effect of myriocin was found to be independent of its role in reducing ceramides, but instead, it depends on the lipid droplets surface protein PLIN2. Our findings provide a novel mechanism for how myriocin enhances Mtb clearance in macrophages.

tuberculosis lipid droplets metabolism myriocin PLIN2 host-directed therapy

SCI

英语

通讯

MOST | National Key Research and Development Program of China (NKPs)[2022YFC2302901] ; National Key Research and Development Program of China["82003813","82000017"] ; National Natural Science Foundation of China["2022A1515220034","2022A1515012438","2020A1515111009"] ; Provincial Natural Science Foundation of Guangdong["KQTD20210811090219022","JCYJ20220818095610021","JCY20220530142801003","JCYJ20210324094614038","JCYJ20220530160207015"] ; Shenzhen Science and Technology Innovation Foundation[FTWS2021079] ; Shenzhen High-level Hospital Construction Fund[G2022155]

Microbiology

Microbiology

WOS:001255060000001

AMER SOC MICROBIOLOGY

Web of Science

1.Shenzhen Univ, Dept Pathogen Biol, Guangdong Prov Key Lab Reg Immun & Dis, Med Sch, Shenzhen, Peoples R China
2.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Affiliated Hosp 1,Clin Med Coll 2, Shenzhen, Guangdong, Peoples R China
3.Univ Southern Calif, Dornsife Coll Letters Arts & Sci, Los Angeles, CA USA
4.Gannan Med Univ, Key Lab Prevent & Treatment Cardiovasc & Cerebrova, Minist Educ, Ganzhou, Peoples R China
5.Shenzhen Baoan Hosp, Dept Clin Lab, Shenzhen, Peoples R China
6.Guangdong Med Univ, Dongguan Affiliated Hosp 1, Guangdong Prov Key Lab Med Mol Diag, Dongguan, Peoples R China
7.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Natl Clin Res Ctr Infect Dis, Shenzhen, Peoples R China

Zhang, Ximeng,Ding, Guanggui,Yang, Xirui,et al. Myriocin enhances the clearance of M. tuberculosis by macrophages through the activation of PLIN2[J]. MSPHERE,2024.

Zhang, Ximeng.,Ding, Guanggui.,Yang, Xirui.,Lu, Hailin.,Xu, Yuzhong.,...&Chen, Xinchun.(2024).Myriocin enhances the clearance of M. tuberculosis by macrophages through the activation of PLIN2.MSPHERE.

Zhang, Ximeng,et al."Myriocin enhances the clearance of M. tuberculosis by macrophages through the activation of PLIN2".MSPHERE (2024).