bioRxiv : the preprint server for biology · 2026
An eicosanoid-enriched follicular microenvironment shapes germinal centre immune dynamics in antiretroviral-treated PLWH.
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Georgakis Spiros, Lindsay Helen, Orfanakis Michail, Rinker Jan Lukas, Estrada Perla Mariana Del Rio, Banga Riddhima, Brenna Cloe, Kang Senbai, Torres-Ruiz Fernanda, Villalobos Yara Andrea Luna, Montes de Oca Gonzalo Salgado, Perreau Matthieu, Delporte Mareva, Lambotte Olivier, Dangaj-Laniti Denarda, de Leval Laurence, Vandekerckhove Linos, Ribeiro Susan Pereira, Gottardo Raphael, Petrovas Constantinos
Аннотация
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 (T FH ) and significantly increased follicular CD25 lo/hi Foxp3 hi 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 PGE 2 /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. Keywords: Follicular Helper CD4 cells, HIV, germinal centre, interferons, eicosanoids.