NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells.
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.
Savina
Ariel
A
Institut Curie, INSERM U653, Immunité et Cancer, 26 rue d'Ulm, 75248 Paris, Cedex 05, France.
Jancic
Carolina
C
Hugues
Stephanie
S
Guermonprez
Pierre
P
Vargas
Pablo
P
Moura
Ivan Cruz
IC
Lennon-Duménil
Ana-Maria
AM
Seabra
Miguel C
MC
Raposo
Graça
G
Amigorena
Sebastian
S
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
D000941:Antigens; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases