Extracellular mitochondria drive CD8 T cell dysfunction in trauma by upregulating CD39.
Bacterial Infection
Critical Care
Emergency Medicine
Pneumonia
Journal
Thorax
ISSN: 1468-3296
Titre abrégé: Thorax
Pays: England
ID NLM: 0417353
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
02
08
2021
accepted:
04
04
2022
pubmed:
26
5
2022
medline:
17
1
2023
entrez:
25
5
2022
Statut:
ppublish
Résumé
The increased mortality and morbidity seen in critically injured patients appears associated with systemic inflammatory response syndrome (SIRS) and immune dysfunction, which ultimately predisposes to infection. Mitochondria released by injury could generate danger molecules, for example, ATP, which in turn would be rapidly scavenged by ectonucleotidases, expressed on regulatory immune cells. To determine the association between circulating mitochondria, purinergic signalling and immune dysfunction after trauma. We tested the impact of hepatocyte-derived free mitochondria on blood-derived and lung-derived CD8 T cells in vitro and in experimental mouse models in vivo. In parallel, immune phenotypic analyses were conducted on blood-derived CD8 T cells obtained from trauma patients. Isolated intact mitochondria are functional and generate ATP ex vivo. Extracellular mitochondria perturb CD8 These studies in experimental models and in a cohort of trauma patients reveal important associations between extracellular mitochondria, aberrant purinergic signalling and immune dysfunction. These pathogenic factors with immune exhaustion are linked to SIRS and could be targeted therapeutically.
Identifiants
pubmed: 35613855
pii: thoraxjnl-2021-218047
doi: 10.1136/thoraxjnl-2021-218047
pmc: PMC9691787
mid: NIHMS1816021
doi:
Substances chimiques
Adenosine Triphosphate
8L70Q75FXE
Antigens, CD
0
Biomarkers
0
ENTPD1 protein, human
EC 3.6.1.5
CD39 antigen
EC 3.6.1.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
151-159Subventions
Organisme : NCI NIH HHS
ID : R21 CA164970
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124408
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM136429
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD098363
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK108894
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM116162
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
Références
Injury. 2014 Dec;45(12):2089-95
pubmed: 25304160
Nature. 2018 Jul;559(7713):264-268
pubmed: 29973721
Injury. 2020 Apr;51(4):819-829
pubmed: 32171537
N Engl J Med. 2003 Jan 9;348(2):138-50
pubmed: 12519925
J Trauma Acute Care Surg. 2021 Jan 1;90(1):46-53
pubmed: 33021603
J Thromb Haemost. 2017 Aug;15(8):1655-1667
pubmed: 28561434
Lancet. 2014 Oct 18;384(9952):1455-65
pubmed: 25390327
FASEB J. 2020 Mar;34(3):3616-3630
pubmed: 31957088
Arch Surg. 1991 Jan;126(1):97-9
pubmed: 1985639
Cancer Res. 2018 Jan 1;78(1):115-128
pubmed: 29066514
J Trauma Acute Care Surg. 2017 May;82(5):853-860
pubmed: 28431414
Immunometabolism. 2019;1(1):
pubmed: 31428464
Mitochondrion. 2019 Sep;48:16-30
pubmed: 30771504
J Exp Med. 2007 Jun 11;204(6):1257-65
pubmed: 17502665
Nature. 2014 Nov 20;515(7527):431-435
pubmed: 25383517
JCI Insight. 2021 Oct 22;6(20):
pubmed: 34520397
JAMA. 2016 Feb 23;315(8):801-10
pubmed: 26903338
Cell Cycle. 2018;17(6):712-721
pubmed: 29582715
JCI Insight. 2017 May 4;2(9):
pubmed: 28469075
Am J Respir Cell Mol Biol. 2013 May;48(5):601-9
pubmed: 23349052
Eur J Trauma Emerg Surg. 2018 Jun;44(3):317-324
pubmed: 29797026
Blood. 2014 Oct 2;124(14):2173-83
pubmed: 25082876
Arterioscler Thromb Vasc Biol. 2019 Jun;39(6):1100-1112
pubmed: 31070456
JCI Insight. 2021 Jan 25;6(2):
pubmed: 33320841
Nat Commun. 2015 Nov 09;6:8819
pubmed: 26549640
Crit Care Med. 2020 Feb;48(2):e123-e132
pubmed: 31939811
N Engl J Med. 2012 Dec 13;367(24):2322-33
pubmed: 23234515
Int Immunol. 2002 Jun;14(6):605-13
pubmed: 12039912
J Clin Invest. 2018 Aug 1;128(8):3583-3594
pubmed: 29894310
Nat Immunol. 2018 Apr;19(4):327-341
pubmed: 29507356
J Exp Med. 2011 Dec 19;208(13):2581-90
pubmed: 22110166
Nature. 2010 Mar 4;464(7285):104-7
pubmed: 20203610
PLoS Pathog. 2015 Oct 20;11(10):e1005177
pubmed: 26485519
Am J Surg. 1996 Sep;172(3):291-6
pubmed: 8862088