NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells

被引:675
作者
Savina, Ariel
Jancic, Carolina
Hugues, Stephanie
Guermonprez, Pierre
Vargas, Pablo
Moura, Ivan Cruz
Lennon-Dumenil, Ana-Maria
Seabra, Miguel C.
Raposo, Graca
Amigorena, Sebastian
机构
[1] Inst Curie, INSERM, U653, F-75248 Paris 05, France
[2] Univ London Imperial Coll Sci Technol & Med, Div Biomed Sci, London SW7 2AZ, England
[3] Inst Curie, INSERM, U520, F-75248 Paris 05, France
[4] Inst Curie, CNRS, UMR144, F-75248 Paris 05, France
基金
英国惠康基金;
关键词
D O I
10.1016/j.cell.2006.05.035
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:205 / 218
页数:14
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