PMID- 18678670
OWN - NLM
STAT- MEDLINE
DCOM- 20081016
LR  - 20211020
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 76
IP  - 10
DP  - 2008 Oct
TI  - Cryptococcus neoformans enters the endolysosomal pathway of dendritic cells and 
      is killed by lysosomal components.
PG  - 4764-71
LID - 10.1128/IAI.00660-08 [doi]
AB  - 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.
FAU - Wozniak, Karen L
AU  - Wozniak KL
AD  - Department of Medicine, Division of Infectious Diseases, University of 
      Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
FAU - Levitz, Stuart M
AU  - Levitz SM
LA  - eng
GR  - R01 AI066087-04/AI/NIAID NIH HHS/United States
GR  - R01 AI025780-22/AI/NIAID NIH HHS/United States
GR  - R01 AI025780-23A1/AI/NIAID NIH HHS/United States
GR  - R01 AI066087-03/AI/NIAID NIH HHS/United States
GR  - R01 AI066087/AI/NIAID NIH HHS/United States
GR  - R01 AI025780/AI/NIAID NIH HHS/United States
GR  - R01 AI025780-21/AI/NIAID NIH HHS/United States
GR  - R01 AI25780/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080804
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Antibodies, Fungal)
RN  - 0 (Opsonin Proteins)
RN  - 9007-36-7 (Complement System Proteins)
SB  - IM
MH  - Animals
MH  - Antibodies, Fungal/immunology
MH  - Cells, Cultured
MH  - Complement System Proteins/immunology
MH  - Cryptococcus neoformans/*immunology
MH  - Dendritic Cells/*immunology/*microbiology/ultrastructure
MH  - Endosomes/immunology/*microbiology
MH  - Humans
MH  - Lysosomes/immunology/*microbiology
MH  - Mice
MH  - Microbial Viability
MH  - Microscopy, Confocal
MH  - Microscopy, Electron, Scanning
MH  - Microscopy, Electron, Transmission
MH  - Microscopy, Video
MH  - Opsonin Proteins/immunology
MH  - Phagocytosis
MH  - Time Factors
PMC - PMC2546838
EDAT- 2008/08/06 09:00
MHDA- 2008/10/17 09:00
PMCR- 2009/04/01
CRDT- 2008/08/06 09:00
PHST- 2008/08/06 09:00 [pubmed]
PHST- 2008/10/17 09:00 [medline]
PHST- 2008/08/06 09:00 [entrez]
PHST- 2009/04/01 00:00 [pmc-release]
AID - IAI.00660-08 [pii]
AID - 0660-08 [pii]
AID - 10.1128/IAI.00660-08 [doi]
PST - ppublish
SO  - Infect Immun. 2008 Oct;76(10):4764-71. doi: 10.1128/IAI.00660-08. Epub 2008 Aug 
      4.