PMID- 23074646
OWN - NLM
STAT- MEDLINE
DCOM- 20130610
LR  - 20211021
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 2
DP  - 2012
TI  - Mechanisms of dendritic cell lysosomal killing of Cryptococcus.
PG  - 739
LID - 10.1038/srep00739 [doi]
LID - 739
AB  - Cryptococcus neoformans is an opportunistic pulmonary fungal pathogen that 
      disseminates to the CNS causing fatal meningitis in immunocompromised patients. 
      Dendritic cells (DCs) phagocytose C. neoformans following inhalation. Following 
      uptake, cryptococci translocate to the DC lysosomal compartment and are killed by 
      oxidative and non-oxidative mechanisms. DC lysosomal extracts kill cryptococci in 
      vitro; however, the means of antifungal activity remain unknown. Our studies 
      determined non-oxidative antifungal activity by DC lysosomal extract. We examined 
      DC lysosomal killing of cryptococcal strains, anti-fungal activity of purified 
      lysosomal enzymes, and mechanisms of killing against C. neoformans. Results 
      confirmed DC lysosome fungicidal activity against all cryptococcal serotypes. 
      Purified lysosomal enzymes, specifically cathepsin B, inhibited cryptococcal 
      growth. Interestingly, cathepsin B combined with its enzymatic inhibitors led to 
      enhanced cryptococcal killing. Electron microscopy revealed structural changes 
      and ruptured cryptococcal cell walls following treatment. Finally, additional 
      studies demonstrated that osmotic lysis was responsible for cryptococcal death.
FAU - Hole, Camaron R
AU  - Hole CR
AD  - Department of Biology and The South Texas Center for Emerging Infectious 
      Diseases, The University of Texas at San Antonio, San Antonio, TX, USA.
FAU - Bui, Hoang
AU  - Bui H
FAU - Wormley, Floyd L Jr
AU  - Wormley FL Jr
FAU - Wozniak, Karen L
AU  - Wozniak KL
LA  - eng
GR  - R01 AI071752/AI/NIAID NIH HHS/United States
GR  - R01 AI071752-04/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121016
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antifungal Agents)
RN  - 0 (Cell Extracts)
RN  - 0 (Protease Inhibitors)
RN  - EC 3.4.22.1 (Cathepsin B)
SB  - IM
MH  - Animals
MH  - Antifungal Agents/pharmacology
MH  - Bone Marrow Cells/cytology/drug effects
MH  - Cathepsin B/antagonists & inhibitors/metabolism
MH  - Cell Extracts
MH  - Cell Wall/drug effects/ultrastructure
MH  - Cryptococcus neoformans/drug effects/growth & 
      development/*immunology/ultrastructure
MH  - Dendritic Cells/drug effects/enzymology/*immunology
MH  - Female
MH  - Humans
MH  - Lysosomes/drug effects/enzymology/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microbial Sensitivity Tests
MH  - *Microbial Viability/drug effects
MH  - Osmosis/drug effects
MH  - Protease Inhibitors/pharmacology
MH  - Reproducibility of Results
PMC - PMC3472389
EDAT- 2012/10/18 06:00
MHDA- 2013/06/12 06:00
PMCR- 2012/10/16
CRDT- 2012/10/18 06:00
PHST- 2012/07/11 00:00 [received]
PHST- 2012/09/19 00:00 [accepted]
PHST- 2012/10/18 06:00 [entrez]
PHST- 2012/10/18 06:00 [pubmed]
PHST- 2013/06/12 06:00 [medline]
PHST- 2012/10/16 00:00 [pmc-release]
AID - srep00739 [pii]
AID - 10.1038/srep00739 [doi]
PST - ppublish
SO  - Sci Rep. 2012;2:739. doi: 10.1038/srep00739. Epub 2012 Oct 16.