Journal article
Endocytic membrane repair by ESCRT-III controls antigen export to the cytosol during antigen cross-presentation
M Gros, E Segura, DC Rookhuizen, B Baudon, S Heurtebise-Chrétien, N Burgdorf, M Maurin, EA Kapp, RJ Simpson, P Kozik, JA Villadangos, MJM Bertrand, M Burbage, S Amigorena
Cell Reports | Published : 2022
Abstract
Despite its crucial role in initiation of cytotoxic immune responses, the molecular pathways underlying antigen cross-presentation remain incompletely understood. The mechanism of antigen exit from endocytic compartments into the cytosol is a long-standing matter of controversy, confronting two main models: transfer through specific channels/transporters or rupture of endocytic membranes and leakage of luminal content. By monitoring the occurrence of intracellular damage in conventional dendritic cells (cDCs), we show that cross-presenting cDC1s display more frequent endomembrane injuries and increased recruitment of endosomal sorting complex required for transport (ESCRT)-III, the main repa..
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Funding Acknowledgements
We thank Hans Acha-Orbea for the MutuDCs and the animal facility and the PICT-IBiSA@Pasteur Imaging Facility of Institut Curie, a member of the France Bioimaging National Infrastructure (ANR-10-INBS-04). We thank Philippe Benaroch, Nicolas Manel, Franck Perez, and all members of the Immune Responses to Cancer Laboratory for scientific discussions. We thank Pierre-Emmanuel Bontefor generation of the violin plots in Figure S1A, Maria Bottermann for galectin-3-related protocols, Stephanie Dogniaux for help with molecular biology, and Evan R. Harrell for critical reading of the manuscript. M.G. is supported by a Fondation pour la Recherche Medicale grant (FDT201805005336). S.A. received funding from INSERM, Institut Curie, la Ligue contre le Cancer (Equipe Labellisee Ligue, EL2014.LNCC/SA), Association de Recherche contre le Cancer (ARC), the European Research Council (2013-AdG 340046 DCBIOX), ANR-10-IDEX-0001-02 PSL*, and ANR-11-LABX-0043. M.B. was supported by an ARC postdoctoral fellowship. E.S. was supported by Marie Curie Actions from the European Commission (project 39408). Research in the group of M.J.M.B. is financially supported by the Vlaams Instituut voor Biotechnologie (VIB), Ghent University, and grants from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO) (G035320N, G044518N, G0G6618N, and G0I5722N) and from the Flemish Government to Peter Vandena-beele (Methusalem BOF09/01M00709 and BOF16/MET_V/007). J.A.V. received funding from the National Health and Medical Research Council of Australia. P.K. was supported by the Wellcome Trust (101578/Z/13/Z) and Medical Research Council (MC_UP_1201/26).