title: NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells.
abstract: To initiate adaptative cytotoxic immune responses, proteolytic peptides derived from phagocytosed antigens are presented by dendritic cells (DCs) to CD8+ T lymphocytes through a process called antigen "crosspresentation." The partial degradation of antigens mediated by lysosomal proteases in an acidic environment must be tightly controlled to prevent destruction of potential peptides for T cell recognition. We now describe a specialization of the phagocytic pathway of DCs that allows a fine control of antigen processing. The NADPH oxidase NOX2 is recruited to the DC's early phagosomes and mediates the sustained production of low levels of reactive oxygen species, causing active and maintained alkalinization of the phagosomal lumen. DCs lacking NOX2 show enhanced phagosomal acidification and increased antigen degradation, resulting in impaired crosspresentation. Therefore, NOX2 plays a critical role in conferring DCs the ability to function as specialized phagocytes adapted to process antigens rather than kill pathogens.
authors.affiliation: Institut Curie, INSERM U653, Immunité et Cancer, 26 rue d'Ulm, 75248 Paris, Cedex 05, France.
authors.forename: Ariel
authors.initials: A
authors.lastname: Savina
authors.forename: Carolina
authors.initials: C
authors.lastname: Jancic
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hugues
authors.forename: Pierre
authors.initials: P
authors.lastname: Guermonprez
authors.forename: Pablo
authors.initials: P
authors.lastname: Vargas
authors.forename: Ivan Cruz
authors.initials: IC
authors.lastname: Moura
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Lennon-Duménil
authors.forename: Miguel C
authors.initials: MC
authors.lastname: Seabra
authors.forename: Graça
authors.initials: G
authors.lastname: Raposo
authors.forename: Sebastian
authors.initials: S
authors.lastname: Amigorena
mesh_terms: D000136:Acid-Base Equilibrium / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007111:Immunity, Cellular / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology; D010588:Phagosomes / Q000276:immunology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000941:Antigens; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases