Batf3-dependent cross-priming by splenic CD169+ macrophages provides protective immunity against tumors

François-Xavier Mauvais (Team Peter van Endert, Institut Necker, Paris)

16 janvier 2025

Séminaire

Infos pratiques

12:00 - 13:00
Salle Rosalind Franklin
Professionnel de recherche
Accès mobilité réduite

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.

Publications

  • Cross-presentation by the others. Mauvais FX, van Endert P. Semin Immunol. 2023 May;67:101764. doi: 10.1016/j.smim.2023.101764. 
  • Kinesin-1 regulates antigen cross-presentation through the scission of tubulations from early endosomes in dendritic cells. Belabed M, Mauvais FX, Maschalidi S, Kurowska M, Goudin N, Huang JD, Fischer A, de Saint Basile G, van Endert P, Sepulveda FE, Ménasché G. Nat Commun. 2020 Apr 14;11(1):1817. doi: 10.1038/s41467-020-15692-0.
  • IRAP Endosomes Control Phagosomal Maturation in Dendritic Cells. Weimershaus M*, Mauvais FX*, Evnouchidou I, Lawand M, Saveanu L, van Endert P. Front Cell Dev Biol. 2020 Dec 11;8:585713. doi: 10.3389/fcell.2020.585713. * equal contribution
  • Innate Immune Signals Induce Anterograde Endosome Transport Promoting MHC Class I Cross-Presentation. Weimershaus M*, Mauvais FX*, Saveanu L*, Adiko C, Babdor J, Abramova A, Montealegre S, Lawand M, Evnouchidou I, Huber KJ, Chadt A, Zwick M, Vargas P, Dussiot M, Lennon-Dumenil AM, Brocker T, Al-Hasani H, van Endert P. Cell Rep. 2018 Sep 25;24(13):3568-3581. doi: 10.1016/j.celrep.2018.08.041. * equal contribution
  • IRAP+ endosomes restrict TLR9 activation and signaling. Babdor J, Descamps D, Adiko AC, Tohmé M, Maschalidi S, Evnouchidou I, Vasconcellos LR, De Luca M, Mauvais FX, Garfa-Traore M, Brinkmann MM, Chignard M, Manoury B, Saveanu L. Nat Immunol. 2017 May;18(5):509-518. doi: 10.1038/ni.3711.