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Cited by 98Research on Leishmaniasis StudiesCaveolin-1 and cellular processesTrypanosoma species research and implications

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Role of caveolae in Leishmania chagasi phagocytosis and intracellular survival in macrophages

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Rodriguez, Nilda E., Gaur, Upasna, Wilson, Mary E.·2006·Cellular Microbiology
DOI 10.1111/j.1462-5822.2006.00695.x
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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.

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Metadata

Authors
Rodriguez, N. E., Gaur, U., & Wilson, M. E.
Affiliations
University of Iowa (US)
Corresponding author
Wilson, Mary E.
ORCID
Wilson, Mary E.
Venue
Cellular Microbiology
Publisher
Hindawi Limited
Published
2006-07
Volume
8
Issue
7
Pages
1106-1120
ISSN
  • 1462-5814 (ISSN-L)
  • 1462-5822
DOI
10.1111/j.1462-5822.2006.00695.x
OpenAlex
W2168898323
Cited by
98
References
0
Citations by year
2025: 1 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 11 · 2018: 2 · 2017: 2 · 2016: 7 · 2015: 4 · 2014: 7 · 2013: 2 · 2012: 7
FWCI
5.68
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 3349 d)
Locations
  • Cellular Microbiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Allergy and Infectious Diseases (AI07343, R01AI045540, T32AI07511, R01AI032135, R01AI048822, T32AI007511)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
  • Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
Keywords
caveolae, Leishmania infantum, phagocytosis, macrophages, intracellular survival, membrane cholesterol, methyl-β-cyclodextrin, caveolin-1, GM1 ganglioside, lysosome fusion, phagosome maturation, intracellular replication, lipid rafts, host-parasite interactions
MeSH terms
Animals, Cholera Toxin, Cholesterol, Gangliosides, Kinetics, Lysosomes, Macrophages, Membrane Fusion, Phagocytosis, Leishmania infantum, Microscopy, Confocal, Caveolae, Caveolin 1, Mice

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