ArticlePLoS pathogens2021
Super enhancer-mediated transcription of miR146a-5p drives M2 polarization during Leishmania donovani infection.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Tick saliva reprograms macrophages into immunosuppressive hubs that regulate T-cell immunity in Rhipicephalus microplus infestation.Communications biology · 2026Article
- Profibrotic macrophage populations and cell communications in pulmonary fibrosis.Journal of physiology and biochemistry · 2026Review
- BRD4 modulates antimicrobial defense via non-canonical NRF2 activation in macrophages to confer protection against sepsis.PLoS pathogens · 2026Article
- Natural product-based therapeutic strategies againstFrontiers in microbiology · 2026Review
- Investigation of the Expression Levels of miR-155, miR-133a, and miR-146b in the Serum of Acute and Chronic Forms of Cutaneous Leishmaniasis.Acta parasitologica · 2025Article
- Targeting BRD4 ameliorates experimental emphysema by disrupting super-enhancer in polarized alveolar macrophage.Respiratory research · 2025Article
- MicroRNAs orchestrating host and vector-borne protozoan interactions: bridging immune modulation and cross-species communication.Frontiers in immunology · 2025Review
- Effects of chitosan-titanium dioxide-Glucantime nanoassemblies onIranian journal of basic medical sciences · 2025Article
- Super enhancers as key drivers of gene regulatory networks in normal and malignant hematopoiesis.Frontiers in cell and developmental biology · 2025Review
- Targeting macrophage phenotypes to prevent diseases caused byFrontiers in immunology · 2025Review
- Predicting the Effect of miRNA on Gene Regulation to Foster Translational Multi-Omics Research-A Review on the Role of Super-Enhancers.Non-coding RNA · 2024Review
- Non-coding RNAs in disease: from mechanisms to therapeutics.Nature reviews. Genetics · 2024Review
- Super-enhancer-driven lncRNA LIMD1-AS1 activated by CDK7 promotes glioma progression.Cell death & disease · 2023Article
- MIR222HG attenuates macrophage M2 polarization and allergic inflammation in allergic rhinitis by targeting the miR146a-5p/TRAF6/NF-κB axis.Frontiers in immunology · 2023Article
- The paradigm of intracellular parasite survival and drug resistance in leishmanial parasite through genome plasticity and epigenetics: Perception and future perspective.Frontiers in cellular and infection microbiology · 2023Review
- The pathogenicity and virulence of Leishmania - interplay of virulence factors with host defenses.Virulence · 2022Review
- Bidirectional cytokine-microRNA control: A novel immunoregulatory framework in leishmaniasis.PLoS pathogens · 2022Review
- Leishmania survives by exporting miR-146a from infected to resident cells to subjugate inflammation.Life science alliance · 2022Article
- MicroRNAs as Regulators of Phagocytosis.Cells · 2022Review
- miR-294 and miR-410 Negatively RegulateNon-coding RNA · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The outcome of Leishmania donovani infection depends upon the dynamic interchanges between M1 and M2 macrophages. Information of the involvement of microRNAs (miRNAs) and epigenetic modifiers in regulating macrophage plasticity during L. donovani infection is still elusive. Differential expression analysis of polarization-regulating miRNAs, revealed significant enrichment of miR146a-5p during Leishmania donovani infection. A sustained enrichment of miR146a-5p was observed in both infected bone marrow derived macrophages (BMDMs) and BALB/c mice organs. We found involvement of miR146a-5p in phagocytosis and survivability of parasites. Moreover, miR146a-5pgot enriched in interleukin 4- stimulated BMDMs, indicating its possible involvement in M2 polarization. Upon transfecting BMDMs with miRVANA anti-146a oligos, M2 markers (CCR7, YM-1, FIZZ-1, arginase-1, IL10 and IL4) and transcription factors (p-STAT6 and c/EBPβ) got depleted with concomitant augmentation of M1-polarizing transcription factors (p-STAT1, AP1 and IRF-1), miR146a target genes (TRAF6 and IRAK1), M1 cytokines (IL12 and TNFα), iNOS, nitric oxide, and nuclear translocation of phospho p-65 subunit. Neutralization of intracellular mature miR146a-5p pool in infected BALB/c mice lower organ parasite burden and expressions of M2 markers and IL10 with enrichment of M1 markers like iNOS and IL12. Additionally, we explored the novel role of super enhancer (SE), a cis-acting regulatory component, to enrich miR146a-5p expression during infection. Enhanced expression and nuclear retention of SE components like BET bromodomain 4 (BRD4) and p300 were found in infected BMDMs. Upon silencing BRD4, expressions of miR146a-5p and M2 markers were down regulated and TRAF6, IRAK1 and iNOS levels increased. STRING V.11 based predication and immune precipitation confirmed the strong interaction amongst BRD4, p300 and RNA pol II (RpbI). Chromatin immune precipitation studies suggested the recruitment of BRD4 at the enhancer loci of miR146a-5p gene during infection. Altogether, our findings revealed a novel role of BRD4/p300-depdendent super-enhancer in regulating miR146a expression during L. donovani infection which in turn mediates M2 polarization and immune-suppression.
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