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MiR‐342 controls Mycobacterium tuberculosis susceptibility by modulating inflammation and cell death
Author(s) -
Fu Beibei,
Lin Xiaoyuan,
Tan Shun,
Zhang Rui,
Xue Weiwei,
Zhang Haiwei,
Zhang Shanfu,
Zhao Qingting,
Wang Yu,
Feldman Kelly,
Shi Lei,
Zhang Shaolin,
Nian Weiqi,
Chaitanya Pavani Krishna,
Li Zhifeng,
Wang Xingsheng,
Wu Haibo
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202052252
Subject(s) - zhàng , china , library science , political science , law , computer science
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that places a heavy strain on public health. Host susceptibility to Mtb is modulated by macrophages, which regulate the balance between cell apoptosis and necrosis. However, the role of molecular switches that modulate apoptosis and necrosis during Mtb infection remains unclear. Here, we show that Mtb‐susceptible mice and TB patients have relatively low miR‐342‐3p expression, while mice with miR‐342‐3p overexpression are more resistant to Mtb. We demonstrate that the miR‐342‐3p/SOCS6 axis regulates anti‐Mtb immunity by increasing the production of inflammatory cytokines and chemokines. Most importantly, the miR‐342‐3p/SOCS6 axis participates in the switching between Mtb‐induced apoptosis and necrosis through A20‐mediated K48‐linked ubiquitination and RIPK3 degradation. Our findings reveal several strategies by which the host innate immune system controls intracellular Mtb growth via the miRNA‐mRNA network and pave the way for host‐directed therapies targeting these pathways.