Identification of drug candidates targeting monocyte reprogramming in people living with HIV.

Autor:	Knoll R; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.; Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany., Bonaguro L; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.; Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany., Dos Santos JC; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands., Warnat-Herresthal S; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.; Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany., Jacobs-Cleophas MCP; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands., Blümel E; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany., Reusch N; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany., Horne A; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.; Systems Hematology, Stem Cells & Precision Medicine, Max Delbrück Center - Berlin Institute for Medical Systems Biology (MDCBIMSB), Berlin, Germany., Herbert M; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.; In Vivo Cell Biology of Infection, Max Planck Institute for Infection Biology (MPIIB), Berlin, Germany., Nuesch-Germano M; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany., Otten T; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands., van der Heijden WA; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands., van de Wijer L; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands., Shalek AK; Broad Institute at Massachusetts Institute of Technology (MIT) and Harvard, Boston, MA, United States.; Ragon Institute of Mass General Hospital (MGH), MIT, and Harvard, Cambridge, MA, United States.; Department of Chemistry, Institute for Medical Engineering and Science, Koch Institute, Cambridge, MA, United States., Händler K; Platform for Single Cell Genomics and Epigenomics (PRECISE), DZNE and University of Bonn, Bonn, Germany.; Institute for Human Genetics, University Hospital Schleswig-Holstein, Lübeck, Germany., Becker M; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany., Beyer MD; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.; Platform for Single Cell Genomics and Epigenomics (PRECISE), DZNE and University of Bonn, Bonn, Germany., Netea MG; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.; Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany., Joosten LAB; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.; Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania., van der Ven AJAM; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands., Schultze JL; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.; Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.; Platform for Single Cell Genomics and Epigenomics (PRECISE), DZNE and University of Bonn, Bonn, Germany., Aschenbrenner AC; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Nov 20; Vol. 14, pp. 1275136. Date of Electronic Publication: 2023 Nov 20 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1275136
Abstrakt:	Introduction: People living with HIV (PLHIV) are characterized by functional reprogramming of innate immune cells even after long-term antiretroviral therapy (ART). In order to assess technical feasibility of omics technologies for application to larger cohorts, we compared multiple omics data layers. Methods: Bulk and single-cell transcriptomics, flow cytometry, proteomics, chromatin landscape analysis by ATAC-seq as well as ex vivo drug stimulation were performed in a small number of blood samples derived from PLHIV and healthy controls from the 200-HIV cohort study. Results: Single-cell RNA-seq analysis revealed that most immune cells in peripheral blood of PLHIV are altered in their transcriptomes and that a specific functional monocyte state previously described in acute HIV infection is still existing in PLHIV while other monocyte cell states are only occurring acute infection. Further, a reverse transcriptome approach on a rather small number of PLHIV was sufficient to identify drug candidates for reversing the transcriptional phenotype of monocytes in PLHIV. Discussion: These scientific findings and technological advancements for clinical application of single-cell transcriptomics form the basis for the larger 2000-HIV multicenter cohort study on PLHIV, for which a combination of bulk and single-cell transcriptomics will be included as the leading technology to determine disease endotypes in PLHIV and to predict disease trajectories and outcomes. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2023 Knoll, Bonaguro, dos Santos, Warnat-Herresthal, Jacobs-Cleophas, Blümel, Reusch, Horne, Herbert, Nuesch-Germano, Otten, van der Heijden, van de Wijer, Shalek, Händler, Becker, Beyer, Netea, Joosten, van der Ven, Schultze and Aschenbrenner.)
Databáze:	MEDLINE
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