TLR-4/microRNA-125a/NF-κB signaling modulates the immune response to Mycobacterium tuberculosis infection

Cell Cycle
Wenyi NiuLigong Zhang

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, could lead to kinds of clinical disorders and remains a leading global health problem, resulting in great morbidity and mortality worldwide. Previous studies have firmly demonstrated that M. tuberculosis (M.tb) has evolved to utilize different mechanisms to evade or attenuate the host immune response, such as regulation of immune-related genes by modulation of miRNAs of host or bacteria. However, the knowledge of functions of miRNAs during M.tb infection remains limited. Here, we reported that a host microRNA, miR-125a, was significantly up-regulated by M.tb infection in both RAW264.7 and THP-1cells, in a TLR4 signaling-dependent manner. Subsequently, our results demonstrated that miR-125a was a negative regulator of NF-kB pathway by directly targeting TRAF6, resulting in the suppression of cytokines, attenuation of immune response and promotion of M.tb survival. Taken together, our findings provide a novel detailed molecular mechanism in which miR-125a was enhanced to inhibit inflammatory cytokines secretion and attenuate the immune response during M.tb infection in RAW264.7 and THP-1 cells, and suggest an intrinsic a promising anti-M.tb therapeutic target.

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Citations

Jun 15, 2019·Journal of Cellular and Molecular Medicine·Xiaofei LiNiancai Peng
Oct 13, 2020·Frontiers in Cellular and Infection Microbiology·Tarina SharmaSeyed Ehtesham Hasnain
Oct 20, 2020·Clinical & Translational Immunology·Prashant ChauhanBhaskar Saha
Oct 26, 2020·Microbial Pathogenesis·Zhaohui WangXiaoling Gao
Apr 13, 2021·Current Microbiology·Priyanka MehtaShibnath Mazumder
Jun 5, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Soudeh Ghafouri-FardMajid Mokhtari
Jun 8, 2021·Frontiers in Immunology·Li WeiBin Zhang
Mar 19, 2021·Dermatology : International Journal for Clinical and Investigative Dermatology·Fang SuWei Liu

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Datasets Mentioned

BETA
GSE29190
GSE52819

Methods Mentioned

BETA
transfection
ELISA
PCR
Assay

Software Mentioned

TargetScan

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