Abstract
To prevent excessive degradation of internalized antigens, which could destroy the peptides recognized by T lymphocytes, dendritic cells have developed several strategies that limit proteolytic activity in phagosomes. The recruitment of the NADPH oxidase NOX2 prevents acidification of phagosomes, limiting antigen degradation. Here, we show that dendritic cells derived from Rab27a-deficient ashen mice show increased phagosome acidification and antigen degradation, causing a defect in antigen cross-presentation. Enhanced acidification results from a delay in the recruitment to phagosomes of a subset of lysosome-related organelles containing the membrane subunits of NOX2. The Rab27a-dependent recruitment of these "inhibitory lysosome-related organelles" to phagosomes continuously limits acidification and degradation of ingested particles in dendritic cells, thus promoting antigen cross-presentation.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Dendritic Cells / cytology
-
Dendritic Cells / metabolism*
-
Dendritic Cells / ultrastructure
-
Flow Cytometry
-
Fluorescent Antibody Technique
-
Green Fluorescent Proteins / genetics
-
Green Fluorescent Proteins / metabolism
-
Hydrogen-Ion Concentration
-
Lysosomal-Associated Membrane Protein 1 / metabolism
-
Lysosomes / metabolism
-
Lysosomes / ultrastructure
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Mice, Transgenic
-
Microscopy, Confocal
-
Microscopy, Immunoelectron
-
NADPH Oxidases / metabolism*
-
Ovalbumin / metabolism
-
Phagosomes / metabolism*
-
Reactive Oxygen Species / metabolism
-
Transfection
-
rab GTP-Binding Proteins / genetics
-
rab GTP-Binding Proteins / metabolism
-
rab GTP-Binding Proteins / physiology*
-
rab27 GTP-Binding Proteins
Substances
-
Lysosomal-Associated Membrane Protein 1
-
Reactive Oxygen Species
-
rab27 GTP-Binding Proteins
-
Green Fluorescent Proteins
-
Ovalbumin
-
NADPH Oxidases
-
Rab27a protein, mouse
-
rab GTP-Binding Proteins