ArticleAmerican journal of respiratory cell and molecular biology2020
Mitochondrial DNA Stimulates TLR9-Dependent Neutrophil Extracellular Trap Formation in Primary Graft Dysfunction.
Article in American journal of respiratory cell and molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 105 citations in OpenAlex.
- Review
- Mitochondria Meet the Lung Microbiome: A Bidirectional Dialogue in Inflammation and Respiratory Diseases.Biomedicines · 2026Review
- Review
- Mitochondrial lipid remodeling in sepsis-associated acute kidney injury: a cardiolipin-centered convergence framework.Archives of toxicology · 2026Review
- Mitochondrial DNA regulation of hepatic ischemia-reperfusion injury and intervention strategies.Journal of translational medicine · 2026Review
- Mitochondria as Inducers of Neutrophil Extracellular Traps.Inflammation · 2026Review
- Role and mechanisms of vascular smooth muscle cell phenotypic transition in diabetic macrovascular complications.Biological research · 2026Review
- The role of mitochondrial DNA and RNA in promoting liver disease pathogenesis.Frontiers in cell and developmental biology · 2026Review
- Neutrophil-macrophage crosstalk network in acute lung injury: feedback circuits linking cytokine storm and cell death.Frontiers in cellular and infection microbiology · 2026Review
- Mitochondrial reprogramming of neutrophil extracellular traps in chronic obstructive pulmonary disease and asthma: toward a phenotype-driven therapeutic framework.Frontiers in immunology · 2026Review
- Neutrophil Heterogeneity in Airway Inflammatory Diseases.Inflammation · 2025Review
- Unlocking the potential of uncontrolled DCD in lung transplantation: A review of 2 decades of experience.JHLT open · 2025Review
- Beyond the Blood Cell: The Emerging Role of Cell-Free DNA in Transfusion Medicine.Journal of hematology · 2025Review
- Primary Graft Dysfunction in Lung Transplantation: An Overview of the Molecular Mechanisms.International journal of molecular sciences · 2025Review
- Tollip deficiency enhances mitophagy and reduces STING activation in influenza A virus-infected mice.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Neutrophil extracellular traps in cancer: From mechanisms to treatments.Clinical and translational medicine · 2025Review
- Targeting mitochondrial complex I of CD177Cell reports. Medicine · 2025Article
- Mitochondrial DNA signals driving immune responses: Why, How, Where?Cell communication and signaling : CCS · 2025Review
- Lung allograft dysbiosis associates with immune response and primary graft dysfunction.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2025Article
- Mechanisms and effects of activation of innate immunity by mitochondrial nucleic acids.International immunology · 2025Review
15 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 2 institutions in 1 country.
Funding
Abstract
The immune system is designed to robustly respond to pathogenic stimuli but to be tolerant to endogenous ligands to not trigger autoimmunity. Here, we studied an endogenous damage-associated molecular pattern, mitochondrial DNA (mtDNA), during primary graft dysfunction (PGD) after lung transplantation. We hypothesized that cell-free mtDNA released during lung ischemia-reperfusion triggers neutrophil extracellular trap (NET) formation via TLR9 signaling. We found that mtDNA increases in the BAL fluid of experimental PGD (prolonged cold ischemia followed by orthotopic lung transplantation) and not in control transplants with minimal warm ischemia. The adoptive transfer of mtDNA into the minimal warm ischemia graft immediately before lung anastomosis induces NET formation and lung injury. TLR9 deficiency in neutrophils prevents mtDNA-induced NETs, and TLR9 deficiency in either the lung donor or recipient decreases NET formation and lung injury in the PGD model. Compared with human lung transplant recipients without PGD, severe PGD was associated with high levels of BAL mtDNA and NETs, with evidence of relative deficiency in DNaseI. We conclude that mtDNA released during lung ischemia-reperfusion triggers TLR9-dependent NET formation and drives lung injury. In PGD, DNaseI therapy has a potential dual benefit of neutralizing a major NET trigger (mtDNA) in addition to dismantling pathogenic NETs.
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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.