Endocytic membrane repair by ESCRT-III controls antigen export to the cytosol during antigen cross-presentation - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Cell Reports Année : 2022

Endocytic membrane repair by ESCRT-III controls antigen export to the cytosol during antigen cross-presentation

Résumé

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 repair system for intracellular membranes, relative to cDC2s. Silencing of CHMP2a or CHMP4b, two effector subunits of ESCRT-III, enhances cytosolic antigen export and cross-presentation. This phenotype is partially reversed by chemical inhibition of RIPK3, suggesting that endocytic damage is related to basal activation of the necroptosis pathway. Membrane repair therefore proves crucial in containing antigen export to the cytosol and cross-presentation in cDCs.

Dates et versions

hal-03877482 , version 1 (29-11-2022)

Identifiants

Citer

Marine Gros, Elodie Segura, Derek Rookhuizen, Blandine Baudon, Sandrine Heurtebise-Chrétien, et al.. Endocytic membrane repair by ESCRT-III controls antigen export to the cytosol during antigen cross-presentation. Cell Reports, 2022, 40 (7), pp.111205. ⟨10.1016/j.celrep.2022.111205⟩. ⟨hal-03877482⟩
29 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More