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

• DOI: 10.3389/fimmu.2023.1275136
• Publication Date: 2023-11-22T09:53:17Z
• Authors: Rainer Knoll; Lorenzo Bonaguro; Jéssica C. dos Sa...; Stefanie Warnat-H...; Maartje C. P. Jac...; Edda Blümel; Nico Reusch; Arik Horne; Miriam Herbert; Melanie Nuesch-Ge...; Twan Otten; Wouter A. van der...; Lisa van de Wijer; Alex K. Shalek; Kristian Händler; Matthias Becker; Marc D. Beyer; Mihai G. Netea; Leo A. B. Joosten; Andre J. A. M. va...; Joachim L. Schultze; Anna C. Aschenbre...
• Keywords: Reprogramming; Monocyte; Omics; Mass cytometry

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 omics technologies for application larger cohorts, we compared multiple data layers. Methods Bulk and single-cell transcriptomics, flow cytometry, proteomics, chromatin landscape analysis ATAC-seq as well ex vivo drug stimulation were performed in a small number blood samples derived from PLHIV healthy controls the 200-HIV cohort study. Results Single-cell RNA-seq revealed that most peripheral altered their transcriptomes specific monocyte state previously described acute infection is still existing while other cell states only occurring infection. Further, reverse transcriptome approach on rather was sufficient identify candidates reversing transcriptional phenotype monocytes PLHIV. Discussion These scientific findings technological advancements clinical transcriptomics form basis 2000-HIV multicenter study PLHIV, which combination bulk will be included leading technology determine disease endotypes predict trajectories outcomes.