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STIM1 promotes migration, phagosomal maturation and antigen cross-presentation in dendritic cells

Author

Listed:
  • Paula Nunes-Hasler

    (University of Geneva)

  • Sophia Maschalidi

    (Laboratory of Normal and Pathological Homeostasis of the Immune System, INSERM UMR1163
    Sorbonne Paris Cité, Faculté de médecine Paris Descartes)

  • 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
    Geneva University Hospital)

  • Stéphanie Hugues

    (University of Geneva)

  • Denis Martinvalet

    (University of Geneva)

  • Bénédicte Manoury

    (Sorbonne Paris Cité, Faculté de médecine Paris Descartes
    Institut National de la Santé et de la Recherche Médicale
    Centre National de la Recherche Scientifique)

  • Nicolas Demaurex

    (University of Geneva)

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.

Suggested Citation

  • 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 Ma, 2017. "STIM1 promotes migration, phagosomal maturation and antigen cross-presentation in dendritic cells," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01600-6
    DOI: 10.1038/s41467-017-01600-6
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