QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 14, Issue 9, 3804-3820, September 2003

This Article Full Text Full Text (PDF) All Versions of this Article: E02-12-0830v1 14/9/3804    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coppens, I. Articles by Joiner, K. A. Search for Related Content PubMed PubMed Citation Articles by Coppens, I. Articles by Joiner, K. A.

Host but Not Parasite Cholesterol Controls Toxoplasma Cell Entry by Modulating Organelle Discharge

Isabelle Coppens ^* , and Keith A. Joiner

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8022

Submitted December 17, 2002; Revised March 24, 2003; Accepted April 25, 2003
Monitoring Editor: Keith Mostov

Host cell cholesterol is implicated in the entry and replication of an increasing number of intracellular microbial pathogens. Although uptake of viral particles via cholesterol-enriched caveolae is increasingly well described, the requirement of cholesterol for internalization of eukaryotic pathogens is poorly understood and is likely to be partly organism specific. We examined the role of cholesterol in active host cell invasion by the protozoan parasite Toxoplasma gondii. The parasitophorous vacuole membrane (PVM) surrounding T. gondii contains cholesterol at the time of invasion. Although cholesterol-enriched parasite apical organelles termed rhoptries discharge at the time of cell entry and contribute to PVM formation, surprisingly, rhoptry cholesterol is not necessary for this process. In contrast, host plasma membrane cholesterol is incorporated into the forming PVM during invasion, through a caveolae-independent mechanism. Unexpectedly, depleting host cell plasma membrane cholesterol blocks parasite internalization by reducing the release of rhoptry proteins that are necessary for invasion. Cholesterol back-addition into host plasma membrane reverses this inhibitory effect of depletion on parasite secretion. These data define a new mechanism by which host cholesterol specifically controls entry of an intracellular pathogen.

Abbreviations used: CHO, Chinese hamster ovary; HFF, human foreskin fibroblast; LDL, low-density lipoproteins; MCD, methyl--cyclodextrin; NBD, nitrobenzoxadiazole; NPC, Niemann-Pick type C; PV, parasitophorous vacuole; PVM, parasitophorous vacuole membrane; TEM, transmission electron microscopy.

Present address: Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205-2223.

^* Corresponding author. E-mail address: icoppens{at}jhsph.edu.

This article has been cited by other articles:

				T. M. Johnson, Z. Rajfur, K. Jacobson, and C. J. Beckers Immobilization of the Type XIV Myosin Complex in Toxoplasma gondii Mol. Biol. Cell, August 1, 2007; 18(8): 3039 - 3046. [Abstract] [Full Text] [PDF]

				O. Silvie, S. Charrin, M. Billard, J.-F. Franetich, K. L. Clark, G.-J. van Gemert, R. W. Sauerwein, F. Dautry, C. Boucheix, D. Mazier, et al. Cholesterol contributes to the organization of tetraspanin-enriched microdomains and to CD81-dependent infection by malaria sporozoites J. Cell Sci., May 15, 2006; 119(10): 1992 - 2002. [Abstract] [Full Text] [PDF]

				P. J. Bradley, C. Ward, S. J. Cheng, D. L. Alexander, S. Coller, G. H. Coombs, J. D. Dunn, D. J. Ferguson, S. J. Sanderson, J. M. Wastling, et al. Proteomic Analysis of Rhoptry Organelles Reveals Many Novel Constituents for Host-Parasite Interactions in Toxoplasma gondii J. Biol. Chem., October 7, 2005; 280(40): 34245 - 34258. [Abstract] [Full Text] [PDF]

				J. Mital, M. Meissner, D. Soldati, and G. E. Ward Conditional Expression of Toxoplasma gondii Apical Membrane Antigen-1 (TgAMA1) Demonstrates That TgAMA1 Plays a Critical Role in Host Cell Invasion Mol. Biol. Cell, September 1, 2005; 16(9): 4341 - 4349. [Abstract] [Full Text] [PDF]

				N. Gupta, M. M. Zahn, I. Coppens, K. A. Joiner, and D. R. Voelker Selective Disruption of Phosphatidylcholine Metabolism of the Intracellular Parasite Toxoplasma gondii Arrests Its Growth J. Biol. Chem., April 22, 2005; 280(16): 16345 - 16353. [Abstract] [Full Text] [PDF]

				M. Yang, I. Coppens, S. Wormsley, P. Baevova, H. C. Hoppe, and K. A. Joiner The Plasmodium falciparum Vps4 homolog mediates multivesicular body formation J. Cell Sci., August 1, 2004; 117(17): 3831 - 3838. [Abstract] [Full Text] [PDF]

				J. R. Smith, D. T. Franc, N. S. Carter, D. Zamora, S. R. Planck, and J. T. Rosenbaum Susceptibility of Retinal Vascular Endothelium to Infection with Toxoplasma gondii Tachyzoites Invest. Ophthalmol. Vis. Sci., April 1, 2004; 45(4): 1157 - 1161. [Abstract] [Full Text] [PDF]