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

Virginie Tardif (1, 2, 3) , Sebastián A Riquelme (4) , Séverine Remy (1, 2, 3) , Leandro J Carreño (4) , Claudia M Cortés (5) , Thomas Simon (1, 2, 3) , Marcelo Hill (1, 2, 3) , Cédric Louvet (1, 2, 3) , Claudia A Riedel (5) , Philippe Blancou (1, 2, 3) , Jean-Marie Bach (6) , Christine Chauveau (1, 2, 3) , Susan M Bueno (4) , Ignacio Anegon (1, 2, 3) , Alexis M Kalergis (1, 2, 3, 7)

1 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
2 ITUN - Institut de transplantation urologie-néphrologie
3 UFR MEDECINE - Université de Nantes - UFR de Médecine et des Techniques Médicales
4 Millenium Institute of Immunology and Immunotherapy
5 Millenium Institute of Immunology and Immunotherapy
6 ONIRIS - École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique
7 Departamento de Reumatologia

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.

Mots clés: Carbon monoxide; Cross-presentation; Endocytosis; Heme oxygenase-1; Antigen processing

Domaines: Médecine humaine et pathologie

Virginie Tardif, Sebastián A Riquelme, Séverine Remy, Leandro J Carreño, Claudia M Cortés, et al.. Carbon monoxide decreases endosome-lysosome fusion and inhibits soluble antigen presentation by dendritic cells to T cells. European Journal of Immunology, 2013, 43 (11), pp.2832-2844. ⟨10.1002/eji.201343600⟩. ⟨inserm-02166083⟩