Carbon monoxide decreases endosome–lysosome fusion and inhibits soluble antigen presentation by dendritic cells to T cells.

Authors

  • Virginie Tardif,

    1. INSERM, UMR 1064, Nantes, France
    2. CHU Nantes, ITUN, Nantes, France
    3. Faculté de Médecine, Université de Nantes, Nantes, France
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Sebastián A. Riquelme,

    1. Millenium Institute of Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Séverine Remy,

    1. INSERM, UMR 1064, Nantes, France
    2. CHU Nantes, ITUN, Nantes, France
    3. Faculté de Médecine, Université de Nantes, Nantes, France
    Search for more papers by this author
  • Leandro J. Carreño,

    1. Millenium Institute of Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
    Search for more papers by this author
  • Claudia M. Cortés,

    1. Millenium Institute of Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Santiago, Chile
    Search for more papers by this author
  • Thomas Simon,

    1. INSERM, UMR 1064, Nantes, France
    2. CHU Nantes, ITUN, Nantes, France
    3. Faculté de Médecine, Université de Nantes, Nantes, France
    Search for more papers by this author
  • Marcelo Hill,

    1. INSERM, UMR 1064, Nantes, France
    2. CHU Nantes, ITUN, Nantes, France
    3. Faculté de Médecine, Université de Nantes, Nantes, France
    Search for more papers by this author
  • Cédric Louvet,

    1. INSERM, UMR 1064, Nantes, France
    2. CHU Nantes, ITUN, Nantes, France
    3. Faculté de Médecine, Université de Nantes, Nantes, France
    Search for more papers by this author
  • Claudia A. Riedel,

    1. Millenium Institute of Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Santiago, Chile
    Search for more papers by this author
  • Philippe Blancou,

    1. INSERM, UMR 1064, Nantes, France
    2. CHU Nantes, ITUN, Nantes, France
    3. Faculté de Médecine, Université de Nantes, Nantes, France
    Search for more papers by this author
  • Jean-Marie Bach,

    1. ONIRIS, Nantes, France
    Search for more papers by this author
  • Christine Chauveau,

    1. INSERM, UMR 1064, Nantes, France
    2. CHU Nantes, ITUN, Nantes, France
    3. Faculté de Médecine, Université de Nantes, Nantes, France
    Search for more papers by this author
  • Susan M. Bueno,

    1. Millenium Institute of Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
    Search for more papers by this author
  • Ignacio Anegon,

    Corresponding author
    1. INSERM, UMR 1064, Nantes, France
    2. CHU Nantes, ITUN, Nantes, France
    3. Faculté de Médecine, Université de Nantes, Nantes, France
    • Full correspondence Dr. Alexis M. Kalergis, Millenium Institute of Immunology and Immunotherapy, Facultad de Ciencias Biológicas. Pontificia Universidad Católica de Chile, Santiago 8331010, Chile

      e-mail: akalergis@bio.puc.cl

      Additional correspondence Dr. Ignacio Anegón, INSERM, UMR 1064, Nantes F44093, France

    Search for more papers by this author
    • These authors share senior authorship.

  • Alexis M. Kalergis

    Corresponding author
    1. INSERM, UMR 1064, Nantes, France
    2. CHU Nantes, ITUN, Nantes, France
    3. Faculté de Médecine, Université de Nantes, Nantes, France
    4. Millenium Institute of Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
    5. Departamento de Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
    • Full correspondence Dr. Alexis M. Kalergis, Millenium Institute of Immunology and Immunotherapy, Facultad de Ciencias Biológicas. Pontificia Universidad Católica de Chile, Santiago 8331010, Chile

      e-mail: akalergis@bio.puc.cl

      Additional correspondence Dr. Ignacio Anegón, INSERM, UMR 1064, Nantes F44093, France

    Search for more papers by this author
    • These authors share senior authorship.


Abstract

Heme oxygenase-1 (HO-1) inhibits immune responses and inflammatory reactions via the catabolism of heme into carbon monoxide (CO), Fe2+, and biliverdin. We have previously shown that either induction of HO-1 or treatment with exogenous CO inhibits LPS-induced maturation of dendritic cells (DCs) and protects in vivo and in vitro antigen-specific inflammation. Here, we evaluated the capacity of HO-1 and CO to regulate antigen presentation on MHC class I and MHC class II molecules by LPS-treated DCs. We observed that HO-1 and CO treatment significantly inhibited the capacity of DCs to present soluble antigens to T cells. Inhibition was restricted to soluble OVA protein, as no inhibition was observed for antigenic OVA-derived peptides, bead-bound OVA protein, or OVA as an endogenous antigen. Inhibition of soluble antigen presentation was not due to reduced antigen uptake by DCs, as endocytosis remained functional after HO-1 induction and CO treatment. On the contrary, CO significantly reduced the efficiency of fusion between late endosomes and lysosomes and not by phagosomes and lysosomes. These data suggest that HO-1 and CO can inhibit the ability of LPS-treated DCs to present exogenous soluble antigens to naïve T cells by blocking antigen trafficking at the level of late endosome–lysosome fusion.

Ancillary