Source:http://linkedlifedata.com/resource/pubmed/id/16819964
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
2006-7-5
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pubmed:abstractText |
Caveolae are membrane microdomains enriched in cholesterol, ganglioside M1 (GM1) and caveolin-1. We explored whether caveolae facilitate the entry of Leishmania chagasi into murine macrophages. Transient depletion of macrophage membrane cholesterol by 1 h exposure to methyl-beta-cyclodextrin (MbetaCD) impaired the phagocytosis of non-opsonized and serum-opsonized virulent L. chagasi. In contrast, MbetaCD did not affect the phagocytosis of opsonized attenuated L. chagasi. As early as 5 min after phagocytosis, virulent L. chagasi colocalized with the caveolae markers GM1 and caveolin-1, and colocalization continued for over 48 h. We explored the kinetics of lysosome fusion. Whereas fluorescent-labelled dextran entered macrophage lysosomes by 30 min after addition, localization of L. chagasi in lysosomes was delayed for 24-48 h after phagocytosis. However, after transient depletion of cholesterol from macrophage membrane with MbetaCD, the proportion of L. chagasi-containing phagosomes that fused with lysosomes increased significantly. Furthermore, intracellular replication was impaired in parasites entering after transient cholesterol depletion, even though lipid microdomains were restored by 4 h after treatment. These observations suggest that virulent L. chagasi localize in caveolae during phagocytosis by host macrophages, and that cholesterol-containing macrophage membrane domains, such as caveolae, target parasites to a pathway that promotes delay of lysosome fusion and intracellular survival.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/AI07343,
http://linkedlifedata.com/resource/pubmed/grant/R01 AI032135,
http://linkedlifedata.com/resource/pubmed/grant/R01 AI045540,
http://linkedlifedata.com/resource/pubmed/grant/R01 AI048822,
http://linkedlifedata.com/resource/pubmed/grant/T32 AI07511
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1462-5814
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1106-20
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:16819964-Animals,
pubmed-meshheading:16819964-Caveolae,
pubmed-meshheading:16819964-Caveolin 1,
pubmed-meshheading:16819964-Cholera Toxin,
pubmed-meshheading:16819964-Cholesterol,
pubmed-meshheading:16819964-Gangliosides,
pubmed-meshheading:16819964-Kinetics,
pubmed-meshheading:16819964-Leishmania infantum,
pubmed-meshheading:16819964-Lysosomes,
pubmed-meshheading:16819964-Macrophages,
pubmed-meshheading:16819964-Membrane Fusion,
pubmed-meshheading:16819964-Mice,
pubmed-meshheading:16819964-Microscopy, Confocal,
pubmed-meshheading:16819964-Phagocytosis
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pubmed:year |
2006
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pubmed:articleTitle |
Role of caveolae in Leishmania chagasi phagocytosis and intracellular survival in macrophages.
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pubmed:affiliation |
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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