ArticleScience translational medicine2021
DNA binding to TLR9 expressed by red blood cells promotes innate immune activation and anemia.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07393243 (Does Clear Priming of the Cardiopulmonary Bypass Circuit Reduce Bypass Associated Inflammation in Ventricular Septal Defect Patients?), which is not on this map. Cited by 126 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.
Does Clear Priming of the Cardiopulmonary Bypass Circuit Reduce Bypass Associated Inflammation in Ventricular Septal Defect Patients?
Who cites it
126 citing papers in PubMed, 1 synthesis or guideline pooled it.
- [Chinese guideline for the diagnosis and treatment of adult autoimmune hemolytic anemia (2023)].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2023Guideline
- DNA Receptor Toll-Like Receptor 9 Signaling Pathway Plays a Major Immunomodulatory Role in Neonatal Acute Lung Injury by Inhibiting Inflammatory Response and Oxidative Stress.Cell biochemistry and biophysics · 2025Trial
- Toll-like receptor 9-overexpressing red blood cell biomimetic microbubbles adsorb cell-free DNA to relieve steatotic liver ischemia-reperfusion injury.Materials today. Bio · 2026Article
- Immune regulation by erythroid cells: how erythroid progenitor cells and mature red blood cells shape immunity.Nature reviews. Immunology · 2026Review
- Erythrocyte-inspired biomaterials for cancer immunotherapy: Integration within the cancer-immunity cycle.Materials today. Bio · 2026Review
- Yigongsan decoction ameliorates anemia of chronic disease by attenuating mothers against decapentaplegic homolog-signal transducer and activator of transcription 3 interaction to regulate iron homeostasis.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Curcumin's Protective Effects Against HMolecules (Basel, Switzerland) · 2026Review
- Article
- Splenic erythrophagocytosis is regulated by ALX/FPR2 signaling.Haematologica · 2026Article
- Tumor-derived DNA drives cancer-associated anemia by promoting reticulocyte clearance.Signal transduction and targeted therapy · 2026Article
- Article
- Functional xenogeneic hematopoietic cells maintaining donor-dominant identity and immune tolerance enable therapy.Experimental hematology & oncology · 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
- 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
- Red Blood Cells Internalize Extracellular DNA via Apoptotic Bodies with Clinical Relevance to Cancer Patients.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Comprehensive Human Red Blood Cell Membrane and Cytoplasmic Proteome Analyses.Scientific data · 2026Article
- Can baseline red blood cell distribution width predict outcomes in peripheral T-cell lymphoma patients?Annals of hematology · 2026Article
- Ubiquitination and degradation of CD47 enhances macrophage phagocytosis of hemolytic erythrocytes.iScience · 2026Article
- Integrated Single-Cell and Bulk Transcriptomics Unveils Immune Profiles in Chick Erythroid Cells upon Avian PathogenicAnimals : an open access journal from MDPI · 2026Article
- Transmissible Gastroenteritis Virus Binding to Red Blood Cells Disrupts Iron Homeostasis and Promotes Viral Infection.Veterinary sciences · 2026Article
66 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
17 authors.
Funding
Abstract
Red blood cells (RBCs) are essential for aerobic respiration through delivery of oxygen to distant tissues. However, RBCs are currently considered immunologically inert, and few, if any, secondary functions of RBCs have been identified. Here, we showed that RBCs serve as critical immune sensors through surface expression of the nucleic acid–sensing Toll-like receptor 9 (TLR9). Mammalian RBCs expressed TLR9 on their surface and bound CpG-containing DNA derived from bacteria, plasmodia, and mitochondria. RBC-bound mitochondrial DNA was increased during human and murine sepsis and pneumonia. In vivo, CpG-carrying RBCs drove accelerated erythrophagocytosis and innate immune activation characterized by increased interferon signaling. Erythroid-specific deletion of TLR9 abrogated erythrophagocytosis and decreased local and systemic cytokine production during CpG-induced inflammation and polymicrobial sepsis. Thus, detection and capture of nucleic acid by TLR9-expressing RBCs regulated red cell clearance and inflammatory cytokine production, demonstrating that RBCs function as immune sentinels during pathologic states. Consistent with these findings, RBC-bound mitochondrial DNA was elevated in individuals with viral pneumonia and sepsis secondary to coronavirus disease 2019 (COVID-19) and associated with anemia and severity of disease. These findings uncover a previously unappreciated role of RBCs as critical players in inflammation distinct from their function in gas transport.
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.