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 inThorax Vol. 78; no. 2; pp. 116 - 117
Main Author Devulder, Justine
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LanguageEnglish
Published England BMJ Publishing Group Ltd and British Thoracic Society 01.02.2023
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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
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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  organization: National Heart & Lung Institute, Imperial College London, London, UK
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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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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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StartPage 116
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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