ArticleProceedings of the National Academy of Sciences of the United States of America2011
Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
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Who cites it
142 citing papers in PubMed, 269 citations in OpenAlex.
- Trial
- MicroRNA-1246 regulates macrophage lipid metabolism and is involved in resistance to human Mycobacterium tuberculosis infection.PLoS pathogens · 2026Article
- Role of Exosomes During Mycobacterium Tuberculosis Infection: A Double-Edged Sword.Biomedicines · 2026Review
- Novel human monoclonal antibodies with enhanced sensitivity for lipoarabinomannan antigens present in urines of TB patients.bioRxiv : the preprint server for biology · 2026Article
- miR-155 aggravates inflammation in MRSA pneumonia by modulating macrophage polarization.Molecular biology reports · 2025Article
- Curcumin as a promising therapeutic agent for diabetic neuropathy: from molecular mechanisms to functional recovery.Diabetology & metabolic syndrome · 2025Review
- Analysis of Key miRNA/mRNA Functional Axes During Host Dendritic Cell Immune Response toGenes · 2025Article
- Human alveolar macrophage response to Mycobacterium tuberculosis: immune characteristics underlying large inter-individual variability.Communications biology · 2025Article
- Role of Tumor Necrosis Factor in Tuberculosis.Biomolecules · 2025Review
- Metabolic Messengers: small extracellular vesicles.Nature metabolism · 2025Review
- ESAT-6 Modulates Macrophage Apoptosis in Mycobacterium Tuberculosis via lncNEAT1/miR-125b-5p/TNF-α Pathway.Infection and drug resistance · 2025Article
- Epigenetic Mechanisms Induced byInternational journal of molecular sciences · 2024Review
- microRNA hsa-miR-425-5p and hsa-miR-4523 expressions as biomarkers of active pulmonary tuberculosis, latent tuberculosis infection, and lymph node tuberculosis.Non-coding RNA research · 2023Article
- Review
- Evaluation of miR-let-7f, miR-125a, and miR-125b expression levels in sputum and serum samples of Iranians and Afghans with pulmonary tuberculosis.Iranian journal of microbiology · 2023Article
- Differential Expression of miR-146 and miR-155 in Active and Latent Tuberculosis Infection.Iranian journal of public health · 2023Article
- LncRNA AK089514/miR-125b-5p/TRAF6 axis mediates macrophage polarization in allergic asthma.BMC pulmonary medicine · 2023Article
- Capturing the multifaceted function of adipose tissue macrophages.Frontiers in immunology · 2023Review
- Differential expression analysis of miRNAs in macrophage-derived exosomes in the tuberculosis-infected bone microenvironment.Frontiers in microbiology · 2023Article
- Different modalities of host cell death and their impact onAmerican journal of physiology. Cell physiology · 2022Review
82 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
Contact of Mycobacterium tuberculosis (M.tb) with the immune system requires interactions between microbial surface molecules and host pattern recognition receptors. Major M.tb-exposed cell envelope molecules, such as lipomannan (LM), contain subtle structural variations that affect the nature of the immune response. Here we show that LM from virulent M.tb (TB-LM), but not from avirulent Myocobacterium smegmatis (SmegLM), is a potent inhibitor of TNF biosynthesis in human macrophages. This difference in response is not because of variation in Toll-like receptor 2-dependent activation of the signaling kinase MAPK p38. Rather, TB-LM stimulation leads to destabilization of TNF mRNA transcripts and subsequent failure to produce TNF protein. In contrast, SmegLM enhances MAPK-activated protein kinase 2 phosphorylation, which is critical for maintaining TNF mRNA stability in part by contributing microRNAs (miRNAs). In this context, human miRNA miR-125b binds to the 3' UTR region of TNF mRNA and destabilizes the transcript, whereas miR-155 enhances TNF production by increasing TNF mRNA half-life and limiting expression of SHIP1, a negative regulator of the PI3K/Akt pathway. We show that macrophages incubated with TB-LM and live M.tb induce high miR-125b expression and low miR-155 expression with correspondingly low TNF production. In contrast, SmegLM and live M. smegmatis induce high miR-155 expression and low miR-125b expression with high TNF production. Thus, we identify a unique cellular mechanism underlying the ability of a major M.tb cell wall component, TB-LM, to block TNF biosynthesis in human macrophages, thereby allowing M.tb to subvert host immunity and potentially increase its virulence.
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