Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis.


Journal

eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614

Informations de publication

Date de publication:
09 11 2020
Historique:
received: 30 01 2020
accepted: 09 11 2020
pubmed: 10 11 2020
medline: 16 3 2021
entrez: 9 11 2020
Statut: epublish

Résumé

Sepsis is a systemic inflammatory response to infection and a leading cause of death. Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in mucosal tissues that recognize bacterial ligands. We investigated MAIT cells during clinical and experimental sepsis, and their contribution to host responses. In experimental sepsis, MAIT-deficient mice had significantly increased mortality and bacterial load, and reduced tissue-specific cytokine responses. MAIT cells of WT mice expressed lower levels of IFN-γ and IL-17a during sepsis compared to sham surgery, changes not seen in non-MAIT T cells. MAIT cells of patients at sepsis presentation were significantly reduced in frequency compared to healthy donors, and were more activated, with decreased IFN-γ production, compared to both healthy donors and paired 90-day samples. Our data suggest that MAIT cells are highly activated and become dysfunctional during clinical sepsis, and contribute to tissue-specific cytokine responses that are protective against mortality during experimental sepsis.

Identifiants

pubmed: 33164745
doi: 10.7554/eLife.55615
pii: 55615
pmc: PMC7679140
doi:
pii:

Substances chimiques

Biomarkers 0
Cytokines 0
Histocompatibility Antigens Class I 0
Minor Histocompatibility Antigens 0
Mr1 protein, mouse 0
RNA, Messenger 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI130378
Pays : United States
Organisme : NIA NIH HHS
ID : R03 AG040631
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002538
Pays : United States
Organisme : NHLBI NIH HHS
ID : K23 HL092161
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM134331
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG008962
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR002540
Pays : United States
Organisme : CSRD VA
ID : I01 CX001696
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG059892
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG048022
Pays : United States

Informations de copyright

© 2020, Trivedi et al.

Déclaration de conflit d'intérêts

ST, DL, CA, CA, AB, EM, OJ, AT, MM, RC, JH, MR, DL No competing interests declared

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Auteurs

Shubhanshi Trivedi (S)

Division of Infectious Diseases, University of Utah, Salt Lake City, United States.

Daniel Labuz (D)

Division of Infectious Diseases, University of Utah, Salt Lake City, United States.

Cole P Anderson (CP)

Division of Infectious Diseases, University of Utah, Salt Lake City, United States.

Claudia V Araujo (CV)

Molecular Medicine Program, University of Utah, Salt Lake City, United States.

Antoinette Blair (A)

Molecular Medicine Program, University of Utah, Salt Lake City, United States.

Elizabeth A Middleton (EA)

Molecular Medicine Program, University of Utah, Salt Lake City, United States.
Division of Pulmonary and Critical Care, University of Utah, Salt Lake City, United States.

Owen Jensen (O)

Division of Infectious Diseases, University of Utah, Salt Lake City, United States.

Alexander Tran (A)

Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, United States.

Matthew A Mulvey (MA)

Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, United States.

Robert A Campbell (RA)

Molecular Medicine Program, University of Utah, Salt Lake City, United States.
Division of General Internal Medicine, Department of Internal Medicine, University of Utah, Salt Lake City, United States.

J Scott Hale (JS)

Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, United States.

Matthew T Rondina (MT)

Molecular Medicine Program, University of Utah, Salt Lake City, United States.
Division of General Internal Medicine, Department of Internal Medicine, University of Utah, Salt Lake City, United States.
George E. Wahlen VAMC Department of Internal Medicine and GRECC, University of Utah, Salt Lake City, United States.

Daniel T Leung (DT)

Division of Infectious Diseases, University of Utah, Salt Lake City, United States.
Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, United States.

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Classifications MeSH