Rv2346c enhances mycobacterial survival within macrophages by inhibiting TNF-α and IL-6 production via the p38/miRNA/NF-κB pathway

Emerging Microbes & Infections
Jing YaoGanzhu Feng

Abstract

The intracellular survival of Mycobacterium tuberculosis (Mtb) has a central role in the pathogenesis of tuberculosis. Mtb Rv2346c is a member of 6-kDa early secreted antigenic target family of proteins, which are known to inhibit the host immune responses to promote bacillary persistence in macrophages. However, the mechanism through which Rv2346c participates in Mtb pathogenesis is unclear. In the present study, recombinant Rv2346c protein was synthesized and used to treat Bacillus Calmette-Guérin (BCG)-infected macrophages. The results showed that Rv2346c inhibited the proliferation of BCG-infected macrophages and enhanced the survival of BCG in macrophages. Tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were upregulated during BCG infection but downregulated by Rv2346c. Additional experiments showed that nuclear transcription factor-κB (NF-κB) in BCG-infected macrophages induced the production of TNF-α and IL-6. In addition, miR-155 and miR-99b had a suppressive effect on NF-κB, and the expression of these miRNAs was promoted by p38. Furthermore, Rv2346c was shown to decrease the activation of NF-κB, whereas it enhanced the phosphorylation of p38 and the expression of miR-155 and miR-99b. The function of Rv2346c was...Continue Reading

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Citations

Dec 25, 2019·Infection and Immunity·Cinthya Ruiz-TagleMaría Elvira Balcells
Feb 6, 2020·Experimental and Therapeutic Medicine·Pingping FengHongbo Shen
Oct 16, 2019·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Cao RuanJianping Xie
Jan 26, 2021·Frontiers in Cellular and Infection Microbiology·Noëmi Rebecca MeierNicole Ritz
Oct 26, 2020·Microbial Pathogenesis·Zhaohui WangXiaoling Gao
Jun 8, 2021·Frontiers in Immunology·Li WeiBin Zhang

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
reverse-transcription PCR
transfection
PCR
ubiquitination
electrophoresis
Feature Extraction
Assay

Software Mentioned

ImageJ
ImagePro Plus
Feature Extraction
Primer
ImagePro
Miranda
SPSS
GenScript

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