Publication: Metallophilic marginal zone macrophages cross-prime CD8+ T cell-mediated protective immunity against blood-borne tumors.

Publié dans: Immunity 2025 Apr; 58(4): 843-860.e20

Auteurs: Mauvais FX, Hamel Y, Silvin A, Mulder K, Hildner K, Akyol R, Dalod M, Koumantou D, Saveanu L, Garfa M, Cagnard N, Bertocci B, Ginhoux F, van Endert P

Résumé

Splenic metallophilic marginal zone macrophages (MMMs) are positioned to control the dissemination of blood-borne threats. We developed a purification protocol to enable characterization of MMMs phenotypically and transcriptionally. MMM gene expression profile was enriched for pathways associated with CD8+ T cell activation and major histocompatibility complex class I (MHC class I) cross-presentation. In vitro, purified MMMs equaled conventional dendritic cells type 1 (cDC1s) in cross-priming CD8+ T cells to soluble and particulate antigens, yet MMMs employed a distinct vacuolar processing pathway. In vivo biphoton and ex vivo light-sheet imaging showed long-standing contacts with cognate T cells differentiating to effectors. MMMs cross-primed protective CD8+ T cell antitumor responses both by capturing blood-borne tumor antigens and by internalizing tumor cells seeding the spleen. This cross-priming required expression of the transcription factor Batf3 by MMMs but was independent of cDC1-mediated capture of tumor material for cross-presentation or MHC class I-dressing. Thus, MMMs combine control of the dissemination of blood-borne pathogens and tumor materials with the initiation of innate and adaptive responses.

Lien vers Pubmed [PMID] – 40139188

Lien vers le DOI – 10.1016/j.immuni.2025.02.027