ArticlePLoS pathogens2017
MicroRNA 26a (miR-26a)/KLF4 and CREB-C/EBPβ regulate innate immune signaling, the polarization of macrophages and the trafficking of Mycobacterium tuberculosis to lysosomes during infection.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.
- Advances in the research of the role of macrophage/microglia polarization-mediated inflammatory response in spinal cord injury.Frontiers in immunology · 2022Pooled it
- Systematic discovery of immunomodulatory plant-derived nanoparticles reveals RNA-mediated macrophage reprogramming.Bioactive materials · 2026Article
- An Rv1471-expressing chimpanzee adenovirus vaccine confers protection against tuberculosis by inducing alveolar macrophage trained immunity and polyfunctional T-cell responses.Emerging microbes & infections · 2026Article
- Gut Microbiota-Non-Coding RNA Axis in Immune Modulation and Disease: From Mechanisms to Clinical Translation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Integrated bioinformatic identification and translational validation of key biomarkers and therapeutic candidates for preeclampsia-related acute kidney injury.Archives of gynecology and obstetrics · 2026Article
- Macrophage states and polarization duringFrontiers in cellular and infection microbiology · 2026Review
- Shared and distinct responses of human and murine alveolar macrophages and monocyte-derived macrophages to Mycobacterium tuberculosis.ImmunoHorizons · 2025Article
- Evaluation of urinary extracellular vesicles and microRNAs to diagnose urogenital tuberculosis.World journal of experimental medicine · 2025Article
- miRNA let-7-5p present in the extracellular vesicles of Trichinella spiralis newborn larvae inhibits the function of M1-type RAW264.7 macrophages by targeting C/EBPδ.Parasites & vectors · 2025Article
- Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.Molecular oncology · 2025Article
- Extracellular Vesicles from Adipose-Derived Mesenchymal Stem Cells Improve Ligament-Bone Integration After Anterior Cruciate Ligament Primary Repair in Rabbit.Biomolecules · 2025Article
- Non-coding RNA Networks in Infection.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Krüppel-like factor 4 control of immune cell function.Frontiers in immunology · 2025Review
- The role of KLF4 in phagocyte activation during infectious diseases.Frontiers in immunology · 2025Review
- Review
- Targeting BamA, the essential component of theHeliyon · 2024Article
- Therapeutic Targeting of Krüppel-Like Factor 4 and Its Pharmacological Potential in Parkinson's Disease: a Comprehensive Review.Molecular neurobiology · 2024Review
- Diagnostic accuracy ofFrontiers in immunology · 2024Article
- Macrophage-derived extracellular vesicles fromFrontiers in immunology · 2024Article
- Non-coding RNAs in bladder cancer, a bridge between gut microbiota and host?Frontiers in immunology · 2024Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For efficient clearance of Mycobacterium tuberculosis (Mtb), macrophages tilt towards M1 polarization leading to the activation of transcription factors associated with the production of antibacterial effector molecules such as nitric oxide (NO) and proinflammatory cytokines such as interleukin 1 β (IL-1β) and tumor necrosis factor α (TNF-α). At the same time, resolution of inflammation is associated with M2 polarization with increased production of arginase and cytokines such as IL-10. The transcriptional and post-transcriptional mechanisms that govern the balance between M1 and M2 polarization, and bacteria-containing processes such as autophagy and trafficking of Mtb to lysosomes, are incompletely understood. Here we report for the first time, that the transcription factor KLF4 is targeted by microRNA-26a (miR-26a). During Mtb infection, downregulation of miR-26a (observed both ex vivo and in vivo) facilitates upregulation of KLF4 which in turn favors increased arginase and decreased iNOS activity. We further demonstrate that KLF4 prevents trafficking of Mtb to lysosomes. The CREB-C/EBPβ signaling axis also favors M2 polarization. Downregulation of miR-26a and upregulation of C/ebpbeta were observed both in infected macrophages as well as in infected mice. Knockdown of C/ebpbeta repressed the expression of selected M2 markers such as Il10 and Irf4 in infected macrophages. The importance of these pathways is substantiated by observations that expression of miR-26a mimic or knockdown of Klf4 or Creb or C/ebpbeta, attenuated the survival of Mtb in macrophages. Taken together, our results attribute crucial roles for the miR-26a/KLF4 and CREB-C/EBPβsignaling pathways in regulating the survival of Mtb in macrophages. These studies expand our understanding of how Mtb hijacks host signaling pathways to survive in macrophages, and open up new exploratory avenues for host-targeted interventions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.