Meta-Biol

• Pathways

After the fusion of phagosome and lysosome lumen acidity rises and the activity of lysosomal proteases increases, conferring proteolytic ability. However antigens must be spared from complete proteolytic destruction. Dendritic cells (DCs) achieve this by regulating the level of proteolysis and phagosomal acidification. DCs recruit the NADPH oxidase NOX2 to the phagosome and mediate sustained production of low levels of reactive oxygen species (ROS), causing active alkalization of the phagosomal lumen (Savina et al. 2006, Ramachandra et al. 2009). NOX2 consumes oxygen and protons (pumped by V-ATPase or other H+ voltage-gated channels) to produce ROS and this lowers phagosome acidity. This apparently reduces antigen proteolysis to a level that allows processing but does not fully destroy the antigenic peptides, favouring increased MHC-I cross presentation (Ramachandra et al. 2009). Rab27a controls the recruitment of NOX2 to DC phagosomes (Savina et al. 2007).