Talaromyces marneffei suppresses macrophage inflammation by regulating host alternative splicing
-
Published:2023-10-16
Issue:1
Volume:6
Page:
-
ISSN:2399-3642
-
Container-title:Communications Biology
-
language:en
-
Short-container-title:Commun Biol
Author:
Wei WudiORCID, Wang GangORCID, Zhang Hong, Bao Xiuli, An Sanqi, Luo Qiang, He Jinhao, Chen Lixiang, Ning Chuanyi, Lai Jingzhen, Yuan Zongxiang, Chen Rongfeng, Jiang JunjunORCID, Ye LiORCID, Liang HaoORCID
Abstract
AbstractTalaromyces marneffei (T. marneffei) immune escape is essential in the pathogenesis of talaromycosis. It is currently known that T. marneffei achieves immune escape through various strategies. However, the role of cellular alternative splicing (AS) in immune escape remains unclear. Here, we depict the AS landscape in macrophages upon T. marneffei infection via high-throughput RNA sequencing and detect a truncated protein of NCOR2 / SMRT, named NCOR2-013, which is significantly upregulated after T. marneffei infection. Mechanistic analysis indicates that NCOR2-013 forms a co-repression complex with TBL1XR1 / TBLR1 and HDAC3, thereby inhibiting JunB-mediated transcriptional activation of pro-inflammatory cytokines via the inhibition of histone acetylation. Furthermore, we identify TUT1 as the AS regulator that regulates NCOR2-013 production and promotes T. marneffei immune evasion. Collectively, these findings indicate that T. marneffei escapes macrophage killing through TUT1-mediated alternative splicing of NCOR2 / SMRT, providing insight into the molecular mechanisms of T. marneffei immune evasion and potential targets for talaromycosis therapy.
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Reference59 articles.
1. Yilmaz, N., Visagie, C. M., Houbraken, J., Frisvad, J. C. & Samson, R. A. Polyphasic taxonomy of the genus Talaromyces. Stud. Mycol. 78, 175–341 (2014). 2. Vanittanakom, N., Cooper, C. R. Jr., Fisher, M. C. & Sirisanthana, T. Penicillium marneffei infection and recent advances in the epidemiology and molecular biology aspects. Clin. Microbiol. Rev. 19, 95–110 (2006). 3. Limper, A. H., Adenis, A., Le, T. & Harrison, T. S. Fungal infections in HIV/AIDS. Lancet Infect. Dis. 17, e334–e343 (2017). 4. Jiang, J. et al. Effects of talaromyces marneffei infection on mortality of HIV/AIDS patients in southern China: a retrospective cohort study. Clin. Microbiol. Infect. 25, 233–241 (2019). 5. Ning, C. et al. The Global Distribution, Drivers, and Burden of Talaromycosis 1964-2017. Boston, MA, USA., (abstr 749) (2020).
|
|