ArticleAmerican journal of respiratory and critical care medicine2018
Red Blood Cells Homeostatically Bind Mitochondrial DNA through TLR9 to Maintain Quiescence and to Prevent Lung Injury.
Article in American journal of respiratory and critical care medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- Stress and circulating cell-free mitochondrial DNA: A systematic review of human studies, physiological considerations, and technical recommendations.Mitochondrion · 2021Pooled it
- Pooled it
- Low- and moderate-intensity aerobic exercise improves the physiological acclimatization of lowlanders on the Tibetan plateau.European journal of sport science · 2024Trial
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- Mitochondrial transcript abundance in breast cancer circulating tumour cells may reflect both blood-derived transcripts and biological heterogeneity.Clinical & experimental metastasis · 2026Article
- Red blood cells as delivery vessels for exerkines: A novel transfusion-based strategy.Sports medicine and health science · 2026Article
- Loss of erythrocyte sialic acid in sepsis disrupts inhibitory Siglec interactions, driving neutrophil hyperactivation and NET outspread.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Tumor-derived DNA drives cancer-associated anemia by promoting reticulocyte clearance.Signal transduction and targeted therapy · 2026Article
- Extracellular heme:DNA complexes promote oxidative stress and inflammation during lupus-associated hemolysis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Red Blood Cells Internalize Extracellular DNA via Apoptotic Bodies with Clinical Relevance to Cancer Patients.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Altered Erythrocyte Function via TLR9-ox-mtDNA Binding Links Mitochondrial Oxidative Damage to Systemic Inflammation in Multiple Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Examination of the Immunological Role of Toll-Like Receptor 9 on Red Blood Cells.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Cell-free DNA in sepsis: from molecular insights to clinical management.Military Medical Research · 2025Review
- Residual Genetic Material in Mature Red Blood Cells.International journal of molecular sciences · 2025Review
- DNASE1L3 surveils mitochondrial DNA on the surface of distinct mammalian cells.bioRxiv : the preprint server for biology · 2025Article
- Erythrocytes as a Source of Exerkines.International journal of molecular sciences · 2025Review
- Effects of Dietary Rumen-Protected Choline on Stress Alleviation, Antioxidant Modulation, and Haematological, Immunological, and Offspring Performance in Transitioning Goats.Veterinary medicine and science · 2025Article
- Article
- Beyond the Blood Cell: The Emerging Role of Cell-Free DNA in Transfusion Medicine.Journal of hematology · 2025Review
- Donor genetics and storage conditions influence mitochondrial DNA and extracellular vesicle levels in RBC units.JCI insight · 2025Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
rationalePotentially hazardous CpG-containing cell-free mitochondrial DNA (cf-mtDNA) is routinely released into the circulation and is associated with morbidity and mortality in critically ill patients. How the body avoids inappropriate innate immune activation by cf-mtDNA remains unknown. Because red blood cells (RBCs) modulate innate immune responses by scavenging chemokines, we hypothesized that RBCs may attenuate CpG-induced lung inflammation through direct scavenging of CpG-containing DNA.
objectivesTo determine the mechanisms of CpG-DNA binding to RBCs and the effects of RBC-mediated DNA scavenging on lung inflammation.
methodsmtDNA on murine RBCs was measured under basal conditions and after systemic inflammation. mtDNA content on human RBCs from healthy control subjects and trauma patients was measured. Toll-like receptor 9 (TLR9) expression on RBCs and TLR9-dependent binding of CpG-DNA to RBCs were determined. A murine model of RBC transfusion after CpG-DNA-induced lung injury was used to investigate the role of RBC-mediated DNA scavenging in mitigating lung injury in vivo. MEASUREMENTS AND MAIN
resultsUnder basal conditions, RBCs bind CpG-DNA. The plasma-to-RBC mtDNA ratio is low in naive mice and in healthy volunteers but increases after systemic inflammation, demonstrating that the majority of cf-mtDNA is RBC-bound under homeostatic conditions and that the unbound fraction increases during inflammation. RBCs express TLR9 and bind CpG-DNA through TLR9. Loss of TLR9-dependent RBC-mediated CpG-DNA scavenging increased lung injury in vivo.
conclusionsRBCs homeostatically bind mtDNA, and RBC-mediated DNA scavenging is essential in mitigating lung injury after CpG-DNA. Our data suggest a role for RBCs in regulating lung inflammation during disease states where cf-mtDNA is elevated, such as sepsis and trauma.
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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.