Functional specialization of short-lived and long-lived macrophage subsets in human tonsils

Autor: Lamine Alaoui, Javiera Villar, Renaud Leclere, Simon Le Gallou, Francis Relouzat, Henri-Alexandre Michaud, Karin Tarte, Natacha Teissier, Benoît Favier, Mikaël Roussel, Elodie Segura
Přispěvatelé: Institut Curie [Paris], Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Hôpital Robert Debré, Institut National de la Santé et de la Recherche Médicale, CIC IGR-Curie 1428, Institut Curie, ANR-10-LABX-0043, Agence Nationale de la Recherche, 2018-1-PL BIO-01-1, Institut National du Cancer, PJA 20171206249, Fondation ARC pour la Recherche sur le Cancer, 730964, TRANSVAC2 H2020, 666003, ERC Horizon 2020-Marie Sklodowska-Curie Actions, FDT202106013025, Fondation pour la Recherche Médicale
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Experimental Medicine
Journal of Experimental Medicine, 2023, 220 (7), pp.e20230002. ⟨10.1084/jem.20230002⟩
ISSN: 0022-1007
1540-9538
Popis: International audience; Macrophages play a central role in tissue homeostasis and host defense. However, the properties of human macrophages in non-diseased tissues remain poorly understood. Here, we characterized human tonsil macrophages and identified three subsets with distinct phenotype, transcriptome, life cycle, and function. CD36hi macrophages were related to monocytes, while CD36lo macrophages showed features of embryonic origin and CD36int macrophages had a mixed profile. scRNA-seq on non-human primate tonsils showed that monocyte recruitment did not pre-exist an immune challenge. Functionally, CD36hi macrophages were specialized for stimulating T follicular helper cells, by producing Activin A. Combining reconstruction of ligand-receptor interactions and functional assays, we identified stromal cell-derived TNF-α as an inducer of Activin A secretion. However, only CD36hi macrophages were primed for Activin A expression, via the activity of IRF1. Our results provide insight into the heterogeneity of human lymphoid organ macrophages and show that tonsil CD36hi macrophage specialization is the result of both intrinsic features and interaction with stromal cells.
Databáze: OpenAIRE
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