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

Autor:	Svensson Akusjärvi S; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden., Krishnan S; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden., Ambikan AT; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden., Mikaeloff F; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden., Munusamy Ponnan S; HIV Vaccine Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Centre, Seattle, USA., Vesterbacka J; Department of Medicine Huddinge (MedH), Karolinska Institutet, Stockholm., 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., 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., 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., Neogi U; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	AIDS (London, England) [AIDS] 2023 Jun 01; Vol. 37 (7), pp. 1023-1033. Date of Electronic Publication: 2023 Mar 21.
DOI:	10.1097/QAD.0000000000003512
Abstrakt:	Objective: 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). Design: Cross-sectional study. Methods: 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. Results: 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. Conclusions: Our data thus suggest that the myeloid cell populations potentially contribute significantly to the modulated metabolic environment during suppressive HIV-1 infection. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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