Dynamic m6A profiles reveal the role of YTHDC2-TLR2 signaling axis in Talaromyces marneffei infection

被引：6

作者：

Chu, Jiemei ^{[1
,2
,3
]}

Zheng, Ruili ^{[4
]}

Chen, Hubin ^{[1
,2
]}

Chen, Yaxin ^{[5
]}

Lin, Yao ^{[1
,2
]}

Li, Jingyi ^{[1
,2
]}

Wei, Wudi ^{[1
,2
,3
]}

Chen, Rongfeng ^{[1
,2
,3
]}

Deng, Peixue ^{[1
,2
]}

Su, Jinming ^{[1
,2
]}

Jiang, Junjun ^{[1
,2
,3
]}

Ye, Li ^{[1
,2
,3
]}

Liang, Hao ^{[1
,2
,3
]}

An, Sanqi ^{[1
,2
]}

机构：

[1] Guangxi Med Univ, Life Sci Inst, Nanning, Guangxi, Peoples R China

[2] Guangxi Med Univ, Guangxi Collaborat Innovat Ctr Regenerat Med & Med, Nanning, Guangxi, Peoples R China

[3] Guangxi Med Univ, Sch Publ Hlth, Guangxi Key Lab AIDS Prevent & Treatment, Nanning, Guangxi, Peoples R China

[4] Changxing Peoples Hosp Chongming Dist, Dept Lab Med, Shanghai, Peoples R China

[5] Sichuan Univ, West China Hosp, Inst Resp Hlth, Frontiers Sci Ctr Dis Related Mol Network, Chengdu, Sichuan, Peoples R China

来源：

JOURNAL OF MEDICAL VIROLOGY | 2024年 / 96卷 / 02期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

m(6)A; macrophages; Talaromyces marneffei; TLR2; YTHDC2; RNA; PROTEIN;

D O I：

10.1002/jmv.29466

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Talaromyces marneffei (TM) immune evasion is an important factor leading to the high mortality rate of Penicilliosis marneffei. N-6-methyladenosine (m(6)A) plays important roles in host immune response to various pathogen infections, yet its role in TM and HIV/TM coinfection remains largely unexplored. Here we reported genome-wide transcriptional m(6)A profiles of TM mono-infection and HIV/TM coinfection. Our finding revealed dynamic alterations in global m(6)A levels and upregulation of the m(6)A reader YTH N-6-methyladenosine RNA binding protein C2 (YTHDC2) in TM-infected macrophages. Knockdown of YTHDC2 in TM-infected cells showed an elevated expression of TLR2 through m(6)A-dependence, along with upregulation of TNF-alpha and IL1-beta. Overall, we characterized the m(6)A profiles of the host and fungus before and after TM infection, and demonstrated that YTHDC2 mediates the key m(6)A site of TLR2 to exert its function. These findings provide new insights into the underlying mechanisms and novel therapeutic approaches for TM diseases.

引用

页数：11

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