Phagocytosis induces lysosome remodeling and regulated presentation of particulate antigens by activated dendritic cells.
Immunization with particulate Ag effectively induces antitumor and antiviral T cell-mediated immunity. Immature dendritic cells (DCs) efficiently internalize, process, and present a variety of particulate Ags; however, previously published data suggest that both the uptake of soluble Ag through micropinocytosis, and phagocytosis of particulates are significantly curtailed in activated DC populations. In this study, we demonstrate that although macropinocytosis of soluble Ag is diminished following DC activation, subsets of DCs in activated DC populations retain the ability to actively phagocytose particulate Ags. Live cell imaging of activated DCs reveals that phagocytosis of particulates can result in cytoskeletal remodeling and perinuclear lysosome cluster disruption in a time-dependent manner. Interestingly, our results suggest that in activated DC populations, presentation of phagocytosed particulate Ags is dependent on the nature of the activation signal. These results provide direct evidence of functional heterogeneity in DC populations and contribute to the development of particle-based immunization strategies.
Nayak
Jayakar V
JV
Department of Dermatology, Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA 15217, USA.
Hokey
David A
DA
Larregina
Adriana
A
He
Yukai
Y
Salter
Russell D
RD
Watkins
Simon C
SC
Falo
Louis D
LD
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology*; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000276:immunology / Q000502:physiology*; D010873:Pinocytosis; D012995:Solubility
D000941:Antigens