title: Carbon monoxide decreases endosome-lysosome fusion and inhibits soluble antigen presentation by dendritic cells to T cells.
abstract: Heme oxygenase-1 (HO-1) inhibits immune responses and inflammatory reactions via the catabolism of heme into carbon monoxide (CO), Fe(2+) , 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.
authors.affiliation: INSERM, UMR 1064, Nantes, France; CHU Nantes, ITUN, Nantes, France; Faculté de Médecine, Université de Nantes, Nantes, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Tardif
authors.forename: Sebastián A
authors.initials: SA
authors.lastname: Riquelme
authors.forename: Séverine
authors.initials: S
authors.lastname: Remy
authors.forename: Leandro J
authors.initials: LJ
authors.lastname: Carreño
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Cortés
authors.forename: Thomas
authors.initials: T
authors.lastname: Simon
authors.forename: Marcelo
authors.initials: M
authors.lastname: Hill
authors.forename: Cédric
authors.initials: C
authors.lastname: Louvet
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Riedel
authors.forename: Philippe
authors.initials: P
authors.lastname: Blancou
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Bach
authors.forename: Christine
authors.initials: C
authors.lastname: Chauveau
authors.forename: Susan M
authors.initials: SM
authors.lastname: Bueno
authors.forename: Ignacio
authors.initials: I
authors.lastname: Anegon
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Kalergis
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002248:Carbon Monoxide / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D002248:Carbon Monoxide; D010047:Ovalbumin; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Antigen processing; Carbon monoxide; Cross-presentation; Endocytosis; Heme oxygenase-1