Reactive oxygen species production in the phagosome: impact on antigen presentation in dendritic cells.

SIGNIFICANCE: The NADPH oxidase 2 (NOX2) is known to play a major role in innate immunity for several decades. Phagocytic cells provide host defense by ingesting microbes and destroy them by different mechanisms, including the generation of reactive oxygen species (ROS) by NOX2, a process known as oxidative burst. The phagocytic pathway of dendritic cells (DCs), highly adapted to antigen processing, has been shown to display remarkable differences compared to other phagocytes. Contrary to macrophages and neutrophils, the main function of DC phagosomes is antigen presentation rather than pathogen killing or clearance of cell debris. RECENT ADVANCES: In the last few years, it became clear that NOX2 is also involved in the establishment of adaptive immunity. Several studies support the idea of a relationship between antigen presentation and the level of antigen degradation, the latter one being regulated by the pH and ROS within phagosomes. CRITICAL ISSUES: The regulation of phagosomal pH exerted by NOX2, and thereby of the efficacy of antigen cross-presentation in DCs, represents a clear illustration of how NOX2 can influence CD8(+) T lymphocyte responses. In this review, we want to put emphasis on the relationship between ROS generation and antigen processing and presentation, since there is growing evidence that the low levels of ROS generated by DCs play an important role in these processes. FUTURE DIRECTIONS: In the next years, it will be interesting to unravel possible mechanisms involved and to find other possible connections between NOX family members and adaptive immune responses.