ArticleNature2011
TLR signalling augments macrophage bactericidal activity through mitochondrial ROS.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 911 papers.
What it found
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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
911 citing papers in PubMed, 1,594 citations in OpenAlex.
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- African swine fever virus impairs porcine alveolar macrophages bactericidal function by disrupting lysosomal acidification and cathepsin activity.PLoS pathogens · 2026Article
- Mitochondria Meet the Lung Microbiome: A Bidirectional Dialogue in Inflammation and Respiratory Diseases.Biomedicines · 2026Review
- Paeonol and Its Metabolites Alleviate LPS/D-GalN-Induced Acute Liver Injury in Mice: Potential Involvement of NDUFS7 and Macrophage Mitochondrial Function.Antioxidants (Basel, Switzerland) · 2026Article
- Mitochondrial profiling across macrophage states reveals inhibition of IL-4/IL-13 reprogramming by the integrated stress response.Science advances · 2026Article
- Metabolic strategies of Enterobacteriaceae gut colonization.Nature reviews. Microbiology · 2026Review
- The integrated stress response kinase GCN2 prevents ZAKα-Dependent inflammatory hyperactivation in macrophages.The Journal of biological chemistry · 2026Article
- Intranasal Delivery of Gallium-Quercetin Nanoparticles for Multi-Target Ferroptosis Inhibition in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Myeloid GHSR Deficiency Protects Against Endotoxemia via Macrophage Mitochondrial Reprogramming.Biomedicines · 2026Article
- RHOT1/2-driven mitochondrial membrane vesicles confer tumor-homing selectivity and enable in situ cancer vaccination.Nature communications · 2026Article
- Potential mechanisms underlyingmBio · 2026Article
- SHIP blocks (MDP + LPS)-induced synergy in macrophages independent of catalytic activity.Journal of leukocyte biology · 2026Article
- Lactic Acid Bacteria with Probiotic Potential Regulating Macrophages: Mechanisms, Regulatory Features, and Clinical Applications.Probiotics and antimicrobial proteins · 2026Review
851 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
10 authors at 4 institutions in 1 country.
Funding
Abstract
Reactive oxygen species (ROS) are essential components of the innate immune response against intracellular bacteria and it is thought that professional phagocytes generate ROS primarily via the phagosomal NADPH oxidase machinery. However, recent studies have suggested that mitochondrial ROS (mROS) also contribute to mouse macrophage bactericidal activity, although the mechanisms linking innate immune signalling to mitochondria for mROS generation remain unclear. Here we demonstrate that engagement of a subset of Toll-like receptors (TLR1, TLR2 and TLR4) results in the recruitment of mitochondria to macrophage phagosomes and augments mROS production. This response involves translocation of a TLR signalling adaptor, tumour necrosis factor receptor-associated factor 6 (TRAF6), to mitochondria, where it engages the protein ECSIT (evolutionarily conserved signalling intermediate in Toll pathways), which is implicated in mitochondrial respiratory chain assembly. Interaction with TRAF6 leads to ECSIT ubiquitination and enrichment at the mitochondrial periphery, resulting in increased mitochondrial and cellular ROS generation. ECSIT- and TRAF6-depleted macrophages have decreased levels of TLR-induced ROS and are significantly impaired in their ability to kill intracellular bacteria. Additionally, reducing macrophage mROS levels by expressing catalase in mitochondria results in defective bacterial killing, confirming the role of mROS in bactericidal activity. These results reveal a novel pathway linking innate immune signalling to mitochondria, implicate mROS as an important component of antibacterial responses and further establish mitochondria as hubs for innate immune signalling.
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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.