Journal article
Role of caveolae in Leishmania chagasi phagocytosis and intracellular survival in macrophages
Cellular microbiology, Vol.8(7), pp.1106-1120
07/2006
DOI: 10.1111/j.1462-5822.2006.00695.x
PMID: 16819964
Abstract
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.
Details
- Title: Subtitle
- Role of caveolae in Leishmania chagasi phagocytosis and intracellular survival in macrophages
- Creators
- Nilda E Rodríguez - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USAUpasna GaurMary E Wilson
- Resource Type
- Journal article
- Publication Details
- Cellular microbiology, Vol.8(7), pp.1106-1120
- Publisher
- England
- DOI
- 10.1111/j.1462-5822.2006.00695.x
- PMID
- 16819964
- ISSN
- 1462-5814
- eISSN
- 1462-5822
- Grant note
- AI07343 / NIAID NIH HHS R01 AI045540 / NIAID NIH HHS R01 AI032135 / NIAID NIH HHS T32 AI07511 / NIAID NIH HHS R01 AI048822 / NIAID NIH HHS
- Language
- English
- Date published
- 07/2006
- Academic Unit
- Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
- Record Identifier
- 9984001135302771
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