Faculty Publications

Role of Caveolae in Leishmania Chagasi Phagocytosis and Intracellular Survival in Macrophages

Document Type

Article

Journal/Book/Conference Title

Cellular Microbiology

Volume

8

Issue

7

First Page

1106

Last Page

1120

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-β-cyclodextrin (MβCD) impaired the phagocytosis of non-opsonized and serum-opsonized virulent L. chagasi. In contrast, MβCD 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 MβCD, 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. © 2006 The Authors; Journal compilation © 2006 Blackwell Publishing Ltd.

Department

Department of Biology

Original Publication Date

7-1-2006

DOI of published version

10.1111/j.1462-5822.2006.00695.x

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