Role of myeloid cells in system-level immunometabolic dysregulation during prolonged successful HIV-1 treatment.


Journal

AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219

Informations de publication

Date de publication:
01 06 2023
Historique:
medline: 5 5 2023
pubmed: 14 2 2023
entrez: 13 2 2023
Statut: ppublish

Résumé

Why people with HIV-1 on ART (PWH ART ) display convoluted metabolism and immune cell functions during prolonged suppressive therapy is not well evaluated. In this study, we aimed to address this question using multiomics methodologies to investigate immunological and metabolic differences between PWH ART and HIV-1 negative individuals (HC). Cross-sectional study. Untargeted and targeted metabolomics was performed using gas and liquid chromatography/mass spectrometry, and targeted proteomics using Olink inflammation panel on plasma samples. The cellular metabolic state was further investigated using flow cytometry and intracellular metabolic measurement in single-cell populations isolated by EasySep cell isolation. Finally, flow cytometry was performed for deep-immunophenotyping of mononuclear phagocytes. We detected increased levels of glutamate, lactate, and pyruvate by plasma metabolomics and increased inflammatory markers (e.g. CCL20 and CCL7) in PWH ART compared to HC. The metabolite transporter detection by flow cytometry in T cells and monocytes indicated an increased expression of glucose transporter 1 (Glut1) and monocarboxylate transporter 1 (MCT-1) in PWH ART . Single cell-type metabolite measurement identified decreased glucose, glutamate, and lactate in monocytic cell populations in PWH ART . Deep-immunophenotyping of myeloid cell lineages subpopulations showed no difference in cell frequency, but expression levels of CCR5 were increased on classical monocytes and some dendritic cells. Our data thus suggest that the myeloid cell populations potentially contribute significantly to the modulated metabolic environment during suppressive HIV-1 infection.

Identifiants

pubmed: 36779490
doi: 10.1097/QAD.0000000000003512
pii: 00002030-202306010-00002
pmc: PMC10155691
doi:

Substances chimiques

Glutamates 0
Lactates 0

Banques de données

figshare
['10.6084/m9.figshare.19589365']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1023-1033

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

Références

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Auteurs

Sara Svensson Akusjärvi (S)

Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden.

Shuba Krishnan (S)

Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden.

Anoop T Ambikan (AT)

Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden.

Flora Mikaeloff (F)

Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden.

Sivasankaran Munusamy Ponnan (S)

HIV Vaccine Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Centre, Seattle, USA.

Jan Vesterbacka (J)

Department of Medicine Huddinge (MedH), Karolinska Institutet, Stockholm.

Magda Lourda (M)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, ANA Futura, Campus Flemingsberg.
Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

Piotr Nowak (P)

Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden.
Department of Medicine Huddinge (MedH), Karolinska Institutet, Stockholm.

Anders Sönnerborg (A)

Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden.
Department of Medicine Huddinge (MedH), Karolinska Institutet, Stockholm.

Ujjwal Neogi (U)

Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden.

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