Host plasma microenvironment in immunometabolically impaired HIV infection leads to dysregulated monocyte function and synaptic transmission ex vivo

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dc.contributor.authorMikaeloff, Floraen
dc.contributor.authorGelpi, Marcoen
dc.contributor.authorEscós, Alejandraen
dc.contributor.authorWang, Tianqien
dc.contributor.authorGupta, Sohamen
dc.contributor.authorOlofsson, Annaen
dc.contributor.authorAkusjärvi, Sara Svenssonen
dc.contributor.authorSchuster, Sabrinaen
dc.contributor.authorNaval, Prajaktaen
dc.contributor.authorSood, Vikasen
dc.contributor.authorNikouyan, Neginen
dc.contributor.authorKnudsen, Andreas D.en
dc.contributor.authorVestad, Beateen
dc.contributor.authorHøgh, Julieen
dc.contributor.authorHov, Johannes R.en
dc.contributor.authorBenfield, Thomasen
dc.contributor.authorTrøseid, Mariusen
dc.contributor.authorPawar, Vinayen
dc.contributor.authorRucevic, Marijanaen
dc.contributor.authorBenfeitas, Ruien
dc.contributor.authorVégvári, Ákosen
dc.contributor.authorO'Mahony, Liamen
dc.contributor.authorSavai, Rajkumaren
dc.contributor.authorBjörkström, Niklas K.en
dc.contributor.authorLourda, Magdaen
dc.contributor.authorde Magalhães, João Pedroen
dc.contributor.authorWeiss, Siegfrieden
dc.contributor.authorMardinoglu, Adilen
dc.contributor.authorVarshney, Mukesh Kumaren
dc.contributor.authorKarlsson, Annika C.en
dc.contributor.authorSyed, Yasir Ahmeden
dc.contributor.authorNielsen, Susanne D.en
dc.contributor.authorNeogi, Ujjwalen
dc.contributor.funderSwedish Research Councilen
dc.contributor.funderKnut and Alice Wallenberg Foundationen
dc.contributor.funderKarolinska Institituteen
dc.contributor.funderNovo Nordic Foundationen
dc.contributor.funderLundbeck Foundationen
dc.contributor.funderAugustinus Foundationen
dc.contributor.funderRegion Hovedstadenen
dc.contributor.funderRigshospitalet Research Councilen
dc.contributor.funderEngineering and Physical Sciences Research Councilen
dc.contributor.funderHodge Foundationen
dc.contributor.funderMedical Research Foundationen
dc.contributor.funderAzeez Farooki awarden
dc.date.accessioned2025-05-13T08:54:16Z
dc.date.available2025-05-13T08:54:16Z
dc.date.issued2025en
dc.description.abstractRisk stratification using multi-omics data deepens understanding of immunometabolism in successfully treated people with HIV (PWH) is inadequately explained. A personalized medicine approach integrating blood cell transcriptomics, plasma proteomics, and metabolomics is employed to identify the mechanisms of immunometabolic complications in prolonged treated PWH from the COCOMO cohort. Among the PWHs, 44% of PWH are at risk of experiencing immunometabolic complications identified using the network-based patient stratification method. Utilizing advanced machine learning techniques and a Bayesian classifier, five plasma protein biomarkers; Tubulin Folding Cofactor B (TBCB), Gamma-Glutamylcyclotransferase (GGCT), Taxilin Alpha (TXLNA), Pyridoxal Phosphate Binding Protein (PLPBP) and Large Tumor Suppressor Kinase 1 (LATS1) are identified as highly differentially abundant between healthy control (HC)-like and immunometabolically at-risk PWHs (all FDR<10−10). The personalized metabolic models predict metabolic perturbations, revealing disruptions in central carbon metabolic fluxes and host tryptophan metabolism in at-risk phenotype. Functional assays in primary cells and cortical forebrain organoids (FBOs) further validate this. Metabolic perturbations lead to persistent monocyte activation, thereby impairing their functions ex vivo. Furthermore, the chronic inflammatory plasma microenvironment contributes to synaptic dysregulation in FBOs. The endogenous plasma inflammatory microenvironment is responsible for chronic inflammation in treated immunometabolically complicated at-risk PWH who have a higher risk of cardiovascular and neuropsychiatric disorders.en
dc.description.sponsorshipSwedish Research Council (Grant Nos.\u00A02017-01330; 2018\u201306156; 2021-01756); Karolinska Instititute (Grant No.\u00A02-117/2023 to U.N.)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid2416453en
dc.identifier.citationMikaeloff, F., Gelpi, M., Escós, A., Wang, T., Gupta, S., Olofsson, A., Akusjärvi, S.S., Schuster, S., Naval, P., Sood, V. and Nikouyan, N. (2025) 'Host plasma microenvironment in immunometabolically impaired HIV infection leads to dysregulated monocyte function and synaptic transmission ex vivo', Advanced Science, 2416453 (18pp). httop://doi.org/10.1002/advs.202416453en
dc.identifier.doi10.1002/advs.202416453en
dc.identifier.endpage18
dc.identifier.issn21983844en
dc.identifier.issued16
dc.identifier.journaltitleAdvanced Scienceen
dc.identifier.urihttps://hdl.handle.net/10468/17429
dc.identifier.volume12
dc.language.isoenen
dc.publisherJohn Wiley and Sons Incen
dc.rights© 2025, the Author(s). Published by Oxford University Press on behalf of the European Public Health Association.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHIV/AIDSen
dc.subjectIntegrative omicsen
dc.subjectPatient stratificationen
dc.subjectPersonalized metabolic modelsen
dc.titleHost plasma microenvironment in immunometabolically impaired HIV infection leads to dysregulated monocyte function and synaptic transmission ex vivoen
dc.typeArticle (peer reviewed)en
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