Talaromyces marneffei suppresses macrophage inflammation by regulating host alternative splicing.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
16 10 2023
16 10 2023
Historique:
received:
16
05
2023
accepted:
02
10
2023
medline:
23
10
2023
pubmed:
17
10
2023
entrez:
16
10
2023
Statut:
epublish
Résumé
Talaromyces 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.
Identifiants
pubmed: 37845378
doi: 10.1038/s42003-023-05409-6
pii: 10.1038/s42003-023-05409-6
pmc: PMC10579421
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1046Informations de copyright
© 2023. Springer Nature Limited.
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