Monocyte-derived dendritic cells exhibit increased levels of lysosomal proteolysis as compared to other human dendritic cell populations.
BACKGROUND
Fine control of lysosomal degradation for limited processing of internalized antigens is a hallmark of professional antigen presenting cells. Previous work in mice has shown that dendritic cells (DCs) contain lysosomes with remarkably low protease content. Combined with the ability to modulate lysosomal pH during phagocytosis and maturation, murine DCs enhance their production of class II MHC-peptide complexes for presentation to T cells.


RESULTS
In this study we extend these findings to human DCs and distinguish between different subsets of DCs based on their ability to preserve internalized antigen. Whereas DCs derived in vitro from CD34+ hematopoietic progenitor cells or isolated from peripheral blood of healthy donors are protease poor, DCs derived in vitro from monocytes (MDDCs) are more similar to macrophages (M Phis) in protease content. Unlike other DCs, MDDCs also fail to reduce their intralysosomal pH in response to maturation stimuli. Indeed, functional characterization of lysosomal proteolysis indicates that MDDCs are comparable to M Phis in the rapid degradation of antigen while other human DC subtypes are attenuated in this capacity.


CONCLUSIONS
Human DCs are comparable to murine DCs in exhibiting a markedly reduced level of lysosomal proteolysis. However, as an important exception to this, human MDDCs stand apart from all other DCs by a heightened capacity for proteolysis that resembles that of M Phis. Thus, caution should be exercised when using human MDDCs as a model for DC function and cell biology.
McCurley
Nathanael
N
Department of Cell Biology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Mellman
Ira
I
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000166:cytology*; D010447:Peptide Hydrolases / Q000378:metabolism
D018952:Antigens, CD34; D010447:Peptide Hydrolases