Macrophages are phagocytic immune cells providing tissue-adapted and -imprinted homeostatic functions. Among key macrophage populations, splenic metallophilic marginal zone macrophages are positioned to sense and control dissemination of bloodborne threats. However, they have escaped thorough characterization for technical reasons. Using a novel purification protocol, we clearly defined MMMs phenotypically and identified their unique gene expression profile positioned for CD8+ T cell activation and MHC class I cross-presentation. In vitro, we showed that purified MMMs equal conventional dendritic cells type 1 (cDC1s) in cross-priming antigens yet employing 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. Moreover, we showed that MMMs cross-prime protective CD8+ T cell antitumor responses both by capturing blood-borne tumor antigens and by internalizing tumor cells seeding the spleen. Critically, this requires Batf3 expression by MMMs but is independent of cDC1s capturing tumor material for cross-presentation or cross-dressed with MHC-I molecules presenting tumor antigens.

Paris Post-docs seminar series.