Frontiers in Immunology (Nov 2023)
Identification of drug candidates targeting monocyte reprogramming in people living with HIV
- Rainer Knoll,
- Rainer Knoll,
- Lorenzo Bonaguro,
- Lorenzo Bonaguro,
- Jéssica C. dos Santos,
- Jéssica C. dos Santos,
- Stefanie Warnat-Herresthal,
- Stefanie Warnat-Herresthal,
- Maartje C. P. Jacobs-Cleophas,
- Maartje C. P. Jacobs-Cleophas,
- Edda Blümel,
- Nico Reusch,
- Arik Horne,
- Arik Horne,
- Miriam Herbert,
- Miriam Herbert,
- Melanie Nuesch-Germano,
- Twan Otten,
- Twan Otten,
- Wouter A. van der Heijden,
- Wouter A. van der Heijden,
- Lisa van de Wijer,
- Lisa van de Wijer,
- Alex K. Shalek,
- Alex K. Shalek,
- Alex K. Shalek,
- Kristian Händler,
- Kristian Händler,
- Matthias Becker,
- Marc D. Beyer,
- Marc D. Beyer,
- Mihai G. Netea,
- Mihai G. Netea,
- Mihai G. Netea,
- Leo A. B. Joosten,
- Leo A. B. Joosten,
- Leo A. B. Joosten,
- Andre J. A. M. van der Ven,
- Andre J. A. M. van der Ven,
- Joachim L. Schultze,
- Joachim L. Schultze,
- Joachim L. Schultze,
- Anna C. Aschenbrenner
Affiliations
- Rainer Knoll
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- Rainer Knoll
- Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
- Lorenzo Bonaguro
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- Lorenzo Bonaguro
- Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
- Jéssica C. dos Santos
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
- Jéssica C. dos Santos
- Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Stefanie Warnat-Herresthal
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- Stefanie Warnat-Herresthal
- Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
- Maartje C. P. Jacobs-Cleophas
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
- Maartje C. P. Jacobs-Cleophas
- Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Edda Blümel
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- Nico Reusch
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- Arik Horne
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- Arik Horne
- Systems Hematology, Stem Cells & Precision Medicine, Max Delbrück Center - Berlin Institute for Medical Systems Biology (MDCBIMSB), Berlin, Germany
- Miriam Herbert
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- Miriam Herbert
- In Vivo Cell Biology of Infection, Max Planck Institute for Infection Biology (MPIIB), Berlin, Germany
- Melanie Nuesch-Germano
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- Twan Otten
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
- Twan Otten
- Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Wouter A. van der Heijden
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
- Wouter A. van der Heijden
- Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Lisa van de Wijer
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
- Lisa van de Wijer
- Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Alex K. Shalek
- Broad Institute at Massachusetts Institute of Technology (MIT) and Harvard, Boston, MA, United States
- Alex K. Shalek
- Ragon Institute of Mass General Hospital (MGH), MIT, and Harvard, Cambridge, MA, United States
- Alex K. Shalek
- Department of Chemistry, Institute for Medical Engineering and Science, Koch Institute, Cambridge, MA, United States
- Kristian Händler
- 0Platform for Single Cell Genomics and Epigenomics (PRECISE), DZNE and University of Bonn, Bonn, Germany
- Kristian Händler
- 1Institute for Human Genetics, University Hospital Schleswig-Holstein, Lübeck, Germany
- Matthias Becker
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- Marc D. Beyer
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- Marc D. Beyer
- 0Platform for Single Cell Genomics and Epigenomics (PRECISE), DZNE and University of Bonn, Bonn, Germany
- Mihai G. Netea
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
- Mihai G. Netea
- Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Mihai G. Netea
- 2Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
- Leo A. B. Joosten
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
- Leo A. B. Joosten
- Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Leo A. B. Joosten
- 3Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Andre J. A. M. van der Ven
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
- Andre J. A. M. van der Ven
- Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Joachim L. Schultze
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- Joachim L. Schultze
- Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
- Joachim L. Schultze
- 0Platform for Single Cell Genomics and Epigenomics (PRECISE), DZNE and University of Bonn, Bonn, Germany
- Anna C. Aschenbrenner
- Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
- DOI
- https://doi.org/10.3389/fimmu.2023.1275136
- Journal volume & issue
-
Vol. 14
Abstract
IntroductionPeople 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.MethodsBulk 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.ResultsSingle-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.DiscussionThese 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.
Keywords
