bioRxivImmunologyPreprint
An eicosanoid-enriched follicular microenvironment shapes germinal centre immune dynamics in antiretroviral-treated PLWH
Spiros GeorgakisiD, Helen Lindsay, Michail OrfanakisiD, Jan Lukas Rinker, Perla M. Del Río EstradaiD, Riddhima Banga, Cloé BrennaiD, Senbai KangiD, Fernanda Torres-RuiziD, Yara Andrea Luna-Villalobos, Gonzalo Salgado Montes de OcaiD, Matthieu PerreauiD, Mareva DelporteiD, Olivier LambotteiD, Denarda Dangaj LanitiiD, Laurence de LevaliD, Linos VandekerckhoveiD, Susan Pereira RibeiroiD, Raphaël GottardoiD, Constantinos PetrovasiD
Abstract
Delineating the follicular (F) cellular and molecular landscape in HIV infection is essential for understanding neutralizing antibody responses and HIV reservoir maintenance. Multiplex imaging analysis revealed a less differentiated profile for follicular helper CD4 T cells (TFH) and significantly increased follicular CD25lo/hiFoxp3hi T cells in lymph nodes (LNs) from antiretroviral treated (cART) compared to viremic (Vir) people living with HIV (PLWH). Spatial transcriptomics identified distinct inflammatory follicular microenvironments in Vir and cART LNs, characterized by interferon and eicosanoid enrichment, respectively. In an independent cohort, scRNA-sequencing analysis of LN-derived cells revealed an enrichment of eicosanoid-related pathways in follicular immune cell types in non-neutralizers compared to neutralizers PLWH. In vitro infection and in situ multimodal investigation of HIV DNA+ cell microenvironments suggested a potential role of PGE2/Eicosanoids in maintaining viral reservoirs in cART LNs. Our data highlight cellular and molecular factors that could regulate both antibody responses and viral reservoir persistence in PLWH.
- organism: human
- assay: spatial transcriptomics
- assay: scRNA-seq
- research focus: cell type annotation
- research focus: differential expression
- research focus: cell-cell communication
- approach: statistical model
- approach: experimental assay
- Citations
- 0
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- HIV remodels germinal centers through T follicular helper cell loss
Derek R. Jacobs, Faiaz Abdool, … James Porterfield·bioRxiv·Oct 10, 2026
- Selective infection and loss of PRDM1+ LN Tfh cells in uncontrolled HIV infection precludes formation of Tfh reservoirs under ART
Vincent H. Wu, Jayme M.L. Nordin, … Michael R. Betts·bioRxiv·Dec 15, 2025
- Neutralization activity in chronic HIV infection is characterized by a distinct programming of follicular helper CD4 T cells
Eirini Moysi, Ashish A. Sharma, … Constantinos Petrovas·Journal of Clinical InvestigationPeer-reviewed·Jul 14, 2026
- Frequencies of circulating Th1-biased T follicular helper cells in acute HIV-1 infection correlate with the development of HIV-specific antibody responses and lower set point viral load
O. Baiyegunhi, B. Ndlovu, … Z. M. Ndhlovu·Journal of VirologyPeer-reviewed·Aug 1, 2018
- Spatial proteomics reveals CD8+ T cell signatures and cellular niches associated with active HIV-1 replication in lymph nodes
Candace C. Liu, Marta Calvet‐Mirabent, … Enrique Martín‐Gayo·bioRxiv·May 14, 2026
- Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells from HIV+ Controllers and Non-Controllers
A. F. George, X. Luo, … N. R. Roan·bioRxiv·Oct 27, 2021