Mitochondria in diseases: from cell power plants to DAMPs
Advances in medicine and the improvement in controlling haemorrhages following trauma have dramatically increased the survival of many people. However, according to the WHO, trauma still accounts for 10% of deaths and 16% of disabilities worldwide—considerably more than infectious diseases, includin...
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Published in | Thorax Vol. 78; no. 2; pp. 116 - 117 |
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Format | Journal Article |
Language | English |
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England
BMJ Publishing Group Ltd and British Thoracic Society
01.02.2023
BMJ Publishing Group LTD |
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Abstract | Advances in medicine and the improvement in controlling haemorrhages following trauma have dramatically increased the survival of many people. However, according to the WHO, trauma still accounts for 10% of deaths and 16% of disabilities worldwide—considerably more than infectious diseases, including malaria, tuberculosis and HIV.1 Indeed, once bleeding has stopped, some patients develop multiorgan failure often accompanied by systemic inflammatory response syndrome (SIRS).2 SIRS can be triggered by the inflammatory response to blood loss and tissue damage rather than an infection. In that case, SIRS is called sterile sepsis and is thought to be induced by the release of endogenous molecules called damage-associated molecular patterns (DAMPs) from the site of tissue injury by inflammatory cells, including neutrophils and necrotic cells.2 Among DAMPs, mitochondria and mtDNA have generated scientific interest as they provoke a vigorous response and seem to trigger severe illnesses in humans, including SIRS. In their Thorax paper, Tiwari-Heckler et al have developed an elegant study to understand how this essential organelle participates in the immune response observed during SIRS.3 |
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AbstractList | Advances in medicine and the improvement in controlling haemorrhages following trauma have dramatically increased the survival of many people. However, according to the WHO, trauma still accounts for 10% of deaths and 16% of disabilities worldwide—considerably more than infectious diseases, including malaria, tuberculosis and HIV.1 Indeed, once bleeding has stopped, some patients develop multiorgan failure often accompanied by systemic inflammatory response syndrome (SIRS).2 SIRS can be triggered by the inflammatory response to blood loss and tissue damage rather than an infection. In that case, SIRS is called sterile sepsis and is thought to be induced by the release of endogenous molecules called damage-associated molecular patterns (DAMPs) from the site of tissue injury by inflammatory cells, including neutrophils and necrotic cells.2 Among DAMPs, mitochondria and mtDNA have generated scientific interest as they provoke a vigorous response and seem to trigger severe illnesses in humans, including SIRS. In their Thorax paper, Tiwari-Heckler et al have developed an elegant study to understand how this essential organelle participates in the immune response observed during SIRS.3 [...]higher bacterial counts and higher levels of neutrophils were detected in the bronchoalveolar lavage of these mice. The fate of T cells is controlled by a series of checkpoint molecules that regulate the quality and magnitude of T cell immune response.7 Thus, after antigen-specific T cell activation, anergy can be triggered in T cells to avoid immune responses to inappropriate stimuli, and as a result of chronic antigen stimulation, T cell exhaustion and senescence limit T cell response.8 There is compelling evidence that demonstrates the coexistence of T cell anergy, exhaustion and senescence in disease, particularly in cancer. [...]checkpoint molecules and markers that characterise T cell subsets are not mutually exclusive although these subsets are conceptually distinct, they may overlap functionally and phenotypically.9 The association between T cell dysfunction and mitochondria could be strengthened using a mouse model where the effect of mitochondria on T cells would be inhibited. [...]the proportion of exhausted T cells (CD39+ or PD-1/Tim3+) was increased in the peripheral blood of trauma patients compared with control subjects. [...]increased levels of mitochondrial DNA were detected in the plasma of trauma patients compared with control subjects and correlated with the proportion of peripheral CD39+ CD8 T cells.3 The proportion of exhausted CD8 T cells seems to be further increased in patients developing SIRS compared with trauma patients without SIRS. |
Author | Devulder, Justine |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36261272$$D View this record in MEDLINE/PubMed |
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Cites_doi | 10.1136/thoraxjnl-2021-218047 10.1038/s41577-020-00454-2 10.1016/j.mito.2018.03.002 10.1016/j.mito.2019.02.002 10.1016/S0140-6736(14)60687-5 10.1038/ni.2035 10.1016/j.coi.2012.12.003 10.1182/blood-2014-05-573543 10.3389/fimmu.2018.01330 |
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Copyright | Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ. 2022 Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ. 2023 Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ. |
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References | Tiwari-Heckler, Lee, Harbison (R3) 2023; 78 Lord, Midwinter, Chen (R1) 2014; 384 Ramirez-Barbieri, Moskowitzova, Shin (R6) 2019; 46 Crespo, Sun, Welling (R9) 2013; 25 Miliotis, Nicolalde, Ortega (R4) 2019; 48 Vourc'h, Roquilly, Asehnoune (R2) 2018; 9 Boudreau, Duchez, Cloutier (R5) 2014; 124 Wherry (R7) 2011; 12 ElTanbouly, Noelle (R8) 2021; 21 2024051320304256000_78.2.116.9 2024051320304256000_78.2.116.6 2024051320304256000_78.2.116.5 2024051320304256000_78.2.116.8 2024051320304256000_78.2.116.7 2024051320304256000_78.2.116.2 2024051320304256000_78.2.116.1 2024051320304256000_78.2.116.4 2024051320304256000_78.2.116.3 35613855 - Thorax. 2023 Feb;78(2):151-159 |
References_xml | – volume: 78 start-page: 151 year: 2023 ident: R3 article-title: Extracellular mitochondria drive CD8 T cell dysfunction in trauma by upregulating CD39 publication-title: Thorax doi: 10.1136/thoraxjnl-2021-218047 – volume: 21 start-page: 257 year: 2021 ident: R8 article-title: Rethinking peripheral T cell tolerance: checkpoints across a T cell's journey publication-title: Nat Rev Immunol doi: 10.1038/s41577-020-00454-2 – volume: 46 start-page: 103 year: 2019 ident: R6 article-title: Alloreactivity and allorecognition of syngeneic and allogeneic mitochondria publication-title: Mitochondrion doi: 10.1016/j.mito.2018.03.002 – volume: 48 start-page: 16 year: 2019 ident: R4 article-title: Forms of extracellular mitochondria and their impact in health publication-title: Mitochondrion doi: 10.1016/j.mito.2019.02.002 – volume: 384 start-page: 1455 year: 2014 ident: R1 article-title: The systemic immune response to trauma: an overview of pathophysiology and treatment publication-title: Lancet doi: 10.1016/S0140-6736(14)60687-5 – volume: 12 start-page: 492 year: 2011 ident: R7 article-title: T cell exhaustion publication-title: Nat Immunol doi: 10.1038/ni.2035 – volume: 25 start-page: 214 year: 2013 ident: R9 article-title: T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment publication-title: Curr Opin Immunol doi: 10.1016/j.coi.2012.12.003 – volume: 124 start-page: 2173 year: 2014 ident: R5 article-title: Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation publication-title: Blood doi: 10.1182/blood-2014-05-573543 – volume: 9 year: 2018 ident: R2 article-title: Trauma-Induced damage-associated molecular Patterns-Mediated remote organ injury and immunosuppression in the acutely ill patient publication-title: Front Immunol doi: 10.3389/fimmu.2018.01330 – ident: 2024051320304256000_78.2.116.4 doi: 10.1016/j.mito.2019.02.002 – ident: 2024051320304256000_78.2.116.3 doi: 10.1136/thoraxjnl-2021-218047 – ident: 2024051320304256000_78.2.116.9 doi: 10.1016/j.coi.2012.12.003 – ident: 2024051320304256000_78.2.116.6 doi: 10.1016/j.mito.2018.03.002 – ident: 2024051320304256000_78.2.116.2 doi: 10.3389/fimmu.2018.01330 – ident: 2024051320304256000_78.2.116.1 doi: 10.1016/S0140-6736(14)60687-5 – ident: 2024051320304256000_78.2.116.5 doi: 10.1182/blood-2014-05-573543 – ident: 2024051320304256000_78.2.116.7 doi: 10.1038/ni.2035 – ident: 2024051320304256000_78.2.116.8 doi: 10.1038/s41577-020-00454-2 – reference: 35613855 - Thorax. 2023 Feb;78(2):151-159 |
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Snippet | Advances in medicine and the improvement in controlling haemorrhages following trauma have dramatically increased the survival of many people. However,... [...]higher bacterial counts and higher levels of neutrophils were detected in the bronchoalveolar lavage of these mice. The fate of T cells is controlled by a... |
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SubjectTerms | Antigens Bacteria Bacterial Infection Bacterial infections Critical Care DNA, Mitochondrial Editorial Emergency Medicine HIV Human immunodeficiency virus Humans Infections Lymphocytes Mitochondria Mitochondrial DNA Neutrophils Patients Pneumonia Senescence Trauma |
Title | Mitochondria in diseases: from cell power plants to DAMPs |
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