An eicosanoid-enriched follicular microenvironment shapes germinal centre immune dynamics in antiretroviral-treated PLWH
Year: 2026
Type: preprint
Study design: Observational Study
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 (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.
Authors: Spiros Georgakis, Helen Lindsay, Michail Orfanakis, Jan Lukas Rinker, Perla Mariana Del Rio Estrada, Riddhima Banga, Cloe Brenna, Senbai Kang, Fernanda Torres-Ruiz, Yara Andrea Luna Villalobos, Gonzalo Salgado Montes de Oca, Matthieu Perreau, Mareva Delporte, Olivier Lambotte, Denarda Dangaj-Laniti, Laurence de Leval, Linos Vandekerckhove, Susan Pereira Ribeiro, Raphael Gottardo, Constantinos Petrovas
Institutions: Centre Hospitalier Universitaire Vaudois, University of Lausanne, Emory University, Instituto Nacional de Enfermedades Respiratorias, Ghent University, Inserm, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, CEA Paris-Saclay - Etablissement de Fontenay-aux-roses, Infectious Disease Models and Innovative Therapies, Ludwig Cancer Research
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7213318159