STIM1 promotes migration, phagosomal maturation and antigen cross-presentation in dendritic cells
Paula Nunes-Hasler (),
Sophia Maschalidi,
Carla Lippens,
Cyril Castelbou,
Samuel Bouvet,
Daniele Guido,
Flavien Bermont,
Esen Y. Bassoy,
Nicolas Page,
Doron Merkler,
Stéphanie Hugues,
Denis Martinvalet,
Bénédicte Manoury and
Nicolas Demaurex
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Paula Nunes-Hasler: University of Geneva
Sophia Maschalidi: Laboratory of Normal and Pathological Homeostasis of the Immune System, INSERM UMR1163
Carla Lippens: University of Geneva
Cyril Castelbou: University of Geneva
Samuel Bouvet: University of Geneva
Daniele Guido: University of Geneva
Flavien Bermont: University of Geneva
Esen Y. Bassoy: University of Geneva
Nicolas Page: University of Geneva
Doron Merkler: University of Geneva
Stéphanie Hugues: University of Geneva
Denis Martinvalet: University of Geneva
Bénédicte Manoury: Sorbonne Paris Cité, Faculté de médecine Paris Descartes
Nicolas Demaurex: University of Geneva
Nature Communications, 2017, vol. 8, issue 1, 1-15
Abstract:
Abstract Antigen cross-presentation by dendritic cells (DC) stimulates cytotoxic T cell activation to promote immunity to intracellular pathogens, viruses and cancer. Phagocytosed antigens generate potent T cell responses, but the signalling and trafficking pathways regulating their cross-presentation are unclear. Here, we show that ablation of the store-operated-Ca2+-entry regulator STIM1 in mouse myeloid cells impairs cross-presentation and DC migration in vivo and in vitro. Stim1 ablation reduces Ca2+ signals, cross-presentation, and chemotaxis in mouse bone-marrow-derived DCs without altering cell differentiation, maturation or phagocytic capacity. Phagosomal pH homoeostasis and ROS production are unaffected by STIM1 deficiency, but phagosomal proteolysis and leucyl aminopeptidase activity, IRAP recruitment, as well as fusion of phagosomes with endosomes and lysosomes are all impaired. These data suggest that STIM1-dependent Ca2+ signalling promotes the delivery of endolysosomal enzymes to phagosomes to enable efficient cross-presentation.
Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01600-6
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DOI: 10.1038/s41467-017-01600-6
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