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nature portfolio siinfekel/h-2kb/pe mhc dextramers privacy policy advertising research nature 472 nature social media ova257–264-specific ifnγ-producing cells ifn-γ spot-forming cells reprints h-2kb-restricted ctl epitope act-mova/kb−/− transgenic mice facilitating t-cell responses siinfekl/h2-kb dextramer staining cd8+ t-cell responses wide-field epifluorescence microscope specific pathogen-free conditions cd8+ t-cell response potential t-cell epitopes h-2kb−/− apoptotic cells mitochondrial nadh-ubiquinone oxidoreductase ova257–264-specific ifnγ sfcs increased ag access n-acetyl-l-cysteine n-terminal glutaredoxin domain strong t-cell response ag-presenting cell functions15 pathogen-induced vacuole rupture open 4 siinfekl/h2-kb dextramer+ tlr-l-induced ros production mhc-i-siinfekl dextramers act-mova/ kb−/− mice cd11b-pdca1+cd11clow cells infect antigen-presenting cells phago-lysosome fusion expressing membrane-bound ova sschia647+cd11clowpdca1+ cells allowed macs anti-cd11c labeling reactive oxygen species permissions β-lactamase substrate ccf4 cd11b−pdca1+cd11clow pdcs original author t-cell responses efficient cross-presenting cells pdcs efficiently cross-presented polyclonal anti-ifn-α efficient proteasome-mediated processing

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         headline:Mitochondrial reactive oxygen species regulate the induction of CD8+ T cells by plasmacytoid dendritic cells
         description:Cross-presentation allows exogenous antigen presentation in association with major histocompatibility complex class I molecules, a process crucial for the priming of CD8+ T-cell responses against viruses and tumors. By contrast to conventional dendritic cells (cDC), which cross-present antigens in the steady state, plasmacytoid dendritic cells (pDC) acquire this ability only after stimulation by Toll-like receptor (TLR) ligands. The intracellular pathways accounting for this functional difference are still unknown. Here we show that the induction of cross-presentation by pDCs is regulated by mitochondria through a reactive oxygen species (ROS)-dependent mechanism, involving pH alkalization and antigen protection. The reduction of mitochondrial ROS production dramatically decreases the cross-presentation capacity of pDCs, leading to a strong reduction of their capacity to trigger CD8+ T-cell responses. Our results demonstrate the importance of mitochondrial metabolism in pDC biology, particularly for the induction of adaptive immune responses. Cross-presentation allows exogenous antigens to be presented by the major histocompatibility I pathway. Here the authors show that the inducible cross-presentation by plasmacytoid dendritic cells is modulated by mitochondria-originated reactive oxygen species.
         datePublished:2018-06-08T00:00:00Z
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      headline:Mitochondrial reactive oxygen species regulate the induction of CD8+ T cells by plasmacytoid dendritic cells
      description:Cross-presentation allows exogenous antigen presentation in association with major histocompatibility complex class I molecules, a process crucial for the priming of CD8+ T-cell responses against viruses and tumors. By contrast to conventional dendritic cells (cDC), which cross-present antigens in the steady state, plasmacytoid dendritic cells (pDC) acquire this ability only after stimulation by Toll-like receptor (TLR) ligands. The intracellular pathways accounting for this functional difference are still unknown. Here we show that the induction of cross-presentation by pDCs is regulated by mitochondria through a reactive oxygen species (ROS)-dependent mechanism, involving pH alkalization and antigen protection. The reduction of mitochondrial ROS production dramatically decreases the cross-presentation capacity of pDCs, leading to a strong reduction of their capacity to trigger CD8+ T-cell responses. Our results demonstrate the importance of mitochondrial metabolism in pDC biology, particularly for the induction of adaptive immune responses. Cross-presentation allows exogenous antigens to be presented by the major histocompatibility I pathway. Here the authors show that the inducible cross-presentation by plasmacytoid dendritic cells is modulated by mitochondria-originated reactive oxygen species.
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         name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
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               name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
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            name:INSERM U1041
            address:
               name:INSERM U1041, Paris, France
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      affiliation:
            name:Equipe Labellisée Ligue Contre le Cancer
            address:
               name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
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            name:Equipe Labellisée Ligue Contre le Cancer
            address:
               name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
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               name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
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            address:
               name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
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            name:Dynamique des Interactions Hôte-Pathogène
            address:
               name:Département de Biologie Cellulaire et Infection, Institut Pasteur, Dynamique des Interactions Hôte-Pathogène, Paris, France
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            address:
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               type:PostalAddress
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            name:Roche SAS
            address:
               name:Roche SAS, Boulogne-Billancourt Cedex, France
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            name:Faculté de Médecine Xavier Bichat
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               type:PostalAddress
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      url:http://orcid.org/0000-0003-2140-0540
      affiliation:
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            address:
               name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
               type:PostalAddress
            type:Organization
            name:INSERM U1041
            address:
               name:INSERM U1041, Paris, France
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Gilles Dadaglio
      affiliation:
            name:Equipe Labellisée Ligue Contre le Cancer
            address:
               name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
               type:PostalAddress
            type:Organization
            name:INSERM U1041
            address:
               name:INSERM U1041, Paris, France
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
      name:INSERM U1041, Paris, France
      name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
      name:INSERM U1041, Paris, France
      name:Immunology of Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Australia
      name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
      name:INSERM U1041, Paris, France
      name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
      name:INSERM U1041, Paris, France
      name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
      name:INSERM U1041, Paris, France
      name:Département de Biologie Cellulaire et Infection, Institut Pasteur, Dynamique des Interactions Hôte-Pathogène, Paris, France
      name:INSERM U932, Institut Curie, Paris, France
      name:Roche SAS, Boulogne-Billancourt Cedex, France
      name:INSERM U773-CRB3, Faculté de Médecine Xavier Bichat, Paris, France
      name:Département de Biologie Cellulaire et Infection, Institut Pasteur, Dynamique des Interactions Hôte-Pathogène, Paris, France
      name:INSERM U932, Institut Curie, Paris, France
      name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
      name:INSERM U1041, Paris, France
      name:Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France
      name:INSERM U1041, Paris, France

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