Cryptococcus neoformans enters the endolysosomal pathway of dendritic cells and is killed by lysosomal components
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2008-08-06Keywords
AnimalsAntibodies, Fungal
Cells, Cultured
Complement System Proteins
Cryptococcus neoformans
Dendritic Cells
Endosomes
Humans
Lysosomes
Mice
Microbial Viability
Microscopy, Confocal
Microscopy, Electron, Scanning
Microscopy, Electron, Transmission
Microscopy, Video
Opsonin Proteins
Phagocytosis
Time Factors
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Cryptococcus neoformans is an opportunistic fungal pathogen that primarily causes disease in immunocompromised individuals. Dendritic cells (DCs) can phagocytose C. neoformans, present cryptococcal antigen, and kill C. neoformans. However, early events following C. neoformans phagocytosis by DCs are not well defined. We hypothesized that C. neoformans traffics to the endosome and the lysosome following phagocytosis by DCs and is eventually killed in the lysosome. Murine bone marrow-derived DCs (BMDCs) or human monocyte-derived DCs (HDCs) were incubated with live, encapsulated C. neoformans yeast cells and opsonizing antibody. Following incubation, DCs were intracellularly stained with antibodies against EEA1 (endosome) and LAMP-1 (late endosome/lysosome). As assessed by confocal microscopy, C. neoformans trafficked to endosomal compartments of DCs within 10 min and to lysosomal compartments within 30 min postincubation. For HDCs, the studies were repeated using complement-sufficient autologous plasma for the opsonization of C. neoformans. These data showed results similar to those for antibody opsonization, with C. neoformans localized to endosomes within 20 min and to lysosomes within 60 min postincubation. Additionally, the results of live real-time imaging studies demonstrated that C. neoformans entered lysosomal compartments within 20 min following the initiation of phagocytosis. The results of scanning and transmission electron microscopy demonstrated conventional zipper phagocytosis of C. neoformans by DCs. Finally, lysosomal extracts were purified from BMDCs and incubated with C. neoformans to determine their potential to kill C. neoformans. The extracts killed C. neoformans in a dose-dependent manner. This study shows that C. neoformans enters into endosomal and lysosomal pathways following DC phagocytosis and can be killed by lysosomal components.Source
Infect Immun. 2008 Oct;76(10):4764-71. Epub 2008 Aug 4. Link to article on publisher's siteDOI
10.1128/IAI.00660-08Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39259PubMed ID
18678670Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/IAI.00660-08