PXD077610-1

PXD077610 is an original dataset announced via ProteomeXchange.

Title	Microbiome-Derived Metabolites Shape CD4⁺ T-Cell Differentiation and Immune Aging in Chronic HIV-1 Infection
Description	The role of aromatic gut-derived bacterial metabolites (GDBMs) in shaping immune cell metabolism and function remains poorly explored. Using ex vivo metabolomic profiling of paired plasma and CD4+ T-cells from people living with HIV-1 (PLWH), we identified a network of aromatic GDBMs whose cell-associated abundance, rather than systemic levels, was linked to broad alterations in CD4+ T-cell metabolic and functional states. Among these metabolites, p-cresol sulfate (PCS) emerged as a mechanistic prototype investigated in depth. Ex vivo flow cytometry and single-cell RNA sequencing of CD4+ T-cells stratified by cell-associated PCS levels revealed dose-dependent enrichment of transcriptional programs associated with impaired differentiation capacity, regulatory-like identity, and cellular senescence. Consistently, in vitro transcriptomic and proteomic analyses of PCS-exposed CD4+ T cells demonstrated induction of cell-cycle arrest, mitochondrial dysfunction, and senescence-associated programs, including upregulation of p16 and p21. Integration of these immunometabolic features with measurements of HIV-1 reservoir size in PLWH revealed that CD4+ T-cell states defined by cell-associated GDBMs track with intact proviral DNA levels in vivo. Together, these findings define a microbiome-derived axis that reshapes CD4+ T-cell metabolism and fate and promotes immune aging-associated states in PLWH. Our data suggest that cell-associated GDBMs may foster immunometabolic CD4+ T-cell states previously linked to long-term HIV-1 reservoir persistence in vivo.
HostingRepository	PRIDE
AnnounceDate	2026-06-25
AnnouncementXML	Submission_2026-06-25_14:53:34.888.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Gordon
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-25 16:24:03	ID requested
⏵ 1	2026-06-25 14:53:35	announced

Silva ACD, Flantzer L, Weinberg J, Kyu S, Daley-Bauer L, Santana AC, Talla A, Rittgers AL, Welbourn S, Gordon DE, Tomalka JA, Marconi VC, Jones DP, Younes SA, T-Cell Differentiation and Immune Aging in Chronic HIV-1 Infection. bioRxiv, ():(2026) [pubmed]

10.64898/2026.01.13.699280;

submitter keyword: HIV, p-cresol sulfate, CD4 T cells, gut-derived bacterial metabolite, PCS

Souheil-Antoine Younes
contact affiliation	Emory University School of Medicine, Department of Pathology and Laboratory Medicine, Pathology Advanced Translational Research Unit
contact email	souheil.younes@emory.edu
lab head
David Gordon
contact affiliation	Emory University
contact email	david.ezra.gordon@emory.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077610

PRIDE project URI

• PRIDE
  1. PXD077610
     1. Label: PRIDE project
     2. Name: Microbiome-Derived Metabolites Shape CD4⁺ T-Cell Differentiation and Immune Aging in Chronic HIV-1 Infection