Overcoating of <i>Toxoplasma</i> Parasitophorous Vacuoles with Host Cell Vimentin Type Intermediate Filaments

Halonen, Sandra K.; Weidner, Earl

doi:10.1111/j.1550-7408.1994.tb05936.x

Cited by 75 publications

(49 citation statements)

References 37 publications

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“…Vimentin has been implicated in diverse functions, from structural roles to roles in the cell cycle and mitosis (94), as well as lipid metabolism, particularly in regard to the biology of lipid droplets (76), whose roles in lipid storage and metabolism are the likely link to energy metabolism and mitochondrial function (3). More relevant to this study, vimentin is reorganized around the PV in T. gondii-infected cells (15,38). Vimentin was found to be heavily modulated in the infected cell.…”

Section: Vol 76 2008 Modulation Of the Host Cell Proteome By T Gonmentioning

confidence: 77%

Modulation of the Host Cell Proteome by the Intracellular Apicomplexan ParasiteToxoplasma gondii

et al. 2008

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To investigate how intracellular parasites manipulate their host cell environment at the molecular level, we undertook a quantitative proteomic study of cells following infection with the apicomplexan parasite Toxoplasma gondii. Using conventional two-dimensional electrophoresis, difference gel electrophoresis (DIGE), and mass spectrometry, we identified host proteins that were consistently modulated in expression following infection. We detected modification of protein expression in key metabolic pathways, including glycolysis, lipid and sterol metabolism, mitosis, apoptosis, and structural-protein expression, suggestive of global reprogramming of cell metabolism by the parasite. Many of the differentially expressed proteins had not been previously implicated in the response to the parasite, while others provide important corroborative protein evidence for previously proposed hypotheses of pathogen-cell interactions. Significantly, over one-third of all modulated proteins were mitochondrial, and this was further investigated by DIGE analysis of a mitochondrion-enriched preparation from infected cells. Comparison of our proteomic data with previous transcriptional studies suggested that a complex relationship exits between transcription and protein expression that may be partly explained by posttranslational modifications of proteins and revealed the importance of investigating protein changes when interpreting transcriptional data. To investigate this further, we used phosphatase treatment and DIGE to demonstrate changes in the phosphorylation states of several key proteins following infection. Overall, our findings indicate that the host cell proteome responds in a dramatic way to T. gondii invasion, in terms of both protein expression changes and protein modifications, and reveal a complex and intimate molecular relationship between host and parasite.The obligate intracellular protozoan Toxoplasma gondii has evolved an intimate relationship with its host that extends to the cellular and molecular levels (82, 83). The absolute requirement for invasion of an appropriate host cell in the replication of the parasite suggests that modification of host functions is central to pathogenesis. Intuitively, this subversion of the cell must be a complex process, since host cells are not inherently programmed to provide an environment conducive to pathogens. Host cells have evolved primary lines of defense as countermeasures to pathogen invasion, establishment, and replication. These include elaborate systems, such as the phagolysosomal fusion, reactive oxygen and nitrogen intermediates, the sequestration of nutrients, and even cell suicide (apoptosis), as defenses to limit pathogen growth. The implementation of these systems and the ability of successful pathogens to mitigate their effects are ultimately mediated by changes in both the levels and activities of key proteins. While some of these changes may be transcriptionally regulated and thus potentially revealed by microarray analysis, the true effectors are proteins,...

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Section: Vol 76 2008 Modulation Of the Host Cell Proteome By T Gonmentioning

confidence: 77%

Modulation of the Host Cell Proteome by the Intracellular Apicomplexan ParasiteToxoplasma gondii

et al. 2008

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“…gondii infection causes the reorganization of host intermediate filaments (IFs) and microtubules (MTs) around the PV (Figure 1) [45,46]. IF association with the PVM may provide a fortifying scaffold for this organelle and play a role in positioning the PV close to the nucleus [45].…”

Section: Cytoskeleton and Lysosomesmentioning

confidence: 99%

Host cell manipulation by the human pathogen Toxoplasma gondii

Laliberté

Carruthers

2008

Cell. Mol. Life Sci.

158

123

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Toxoplasma gondii is an obligate intracellular parasite that can infect virtually any nucleated cell. During cell invasion Toxoplasma creates a subcellular compartment termed the parasitophorous vacuole, which acts as an interface between the parasite and host cytoplasm, and in many cases serves as a platform for modulation of several host cell functions that support parasite replication and infection. Spatial reorganization of host organelles and the remodeling of the cytoskeleton around the parasitophorous vacuole are observed early following entry and recent evidence suggests this interior redecorating promotes nutrient acquisition by the parasite. New findings also reveal that T. gondii manipulates signaling pathways of the host cell by deploying parasite kinases and a phosphatase, including at least two that infiltrate the host nucleus. T. gondii infection additionally controls several cellular pathways to establish an anti-apoptotic environment in a variety of cell types, and to subvert immune cells as a conduit for dissemination. In this review we discuss these recent developments in understanding how T. gondii achieves widespread success as a human and animal parasite by manipulating its host.

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“…For example, the Encephalitozoon microsporidia develop within a parasitophorous vacuole and to accommodate the parasites, host cell microtubules reorganize around this vacuole ). In Toxoplasma gondii-infected cells the parasitophorous vacuole is stabilized by a sheath of host cell intermediate filaments (Halonen and Weidner 1994). In the present study it appears that the host cell microtubule cytoskeleton played a major role in organizing the Vittaforma corneae stages and supporting host cell organelles (Fig.…”

Section: Discussionmentioning

confidence: 60%

“…As obligate intracellular parasites the microsporidia appear to have been able to reduce their genome size, simplify their organelle structures and reduce their biochemical pathways by subverting the host cell's physiology to provide the missing biochemical support for parasite development (Slamovits et al 2004). As with other intracellular parasites, from viruses to protozoa (e.g., Halonen and Weidner 1994, Risco et al 2002, Grieshaber et al 2003, the microsporidia appear to modify host cell cytoskeleton, organelle arrangement, biochemistry and cell cycle to optimize the intracellular niche (Weidner et al 1999, Scanlon et al 2000. To date, compared with many other infectious agents, relatively little is known about how the microsporidia signal the host cells to affect these many changes that occur in host cell structure and function.…”

Section: Multinucleate Host Cells Induced By Vittaforma Corneae (Micrmentioning

confidence: 99%

Multinucleate host cells induced by Vittaforma corneae (Microsporidia)

Leitch¹,

Shaw²,

Colden-Stanfield³

et al. 2005

FOLIA PARASIT

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Abstract. The microsporidium Vittaforma corneae (Shadduck, Meccoli, Davis et Font, 1990) develops within the target cell cytoplasm. In the present study, green monkey kidney (E6) cells infected at 30°C, 35°C or 37°C with V. corneae developed enlarged multinucleate structures of up to 200 µm in any horizontal dimension made up either of a single cell or of multiple fused cells. A number of epithelial cell types (SW-480, HT-29, Caco-2 and HCT-8) were infected with V. corneae but did not induce the same highly organized structures, suggesting that for the structure to develop, the host cell must be capable of continued mitosis, and not be differentiated or be detaching from the surface matrix. Live cell imaging of infected E6 cells revealed large, multinucleate infected cells characterized by a central focus from which radiated parasite stages and host cell mitochondria. Immunocytochemistry identifying γ and α tubulin suggested that a single centrally-located microtubule organizing centre governed the distribution of parasite stages and host cell organelles, with mitochondria and parasites being eventually transported towards the periphery of the structure. Whole cell patch clamp analysis of infected cells indicated an average five-fold increase in total membrane capacitance, consistent with an enlarged single cell. Scanning electron microscopy revealed cell-like protrusions around the periphery of the structure with the intervening space being made up of parasites and cell debris. Clearly in the case of V. corneae-infected E6 cells the parasite-host cell relationship involves subverting the host cell cytoskeleton and cell volume control, providing the parasite with the same protected niche as does a xenoma.

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Overcoating of Toxoplasma Parasitophorous Vacuoles with Host Cell Vimentin Type Intermediate Filaments

Cited by 75 publications

References 37 publications

Modulation of the Host Cell Proteome by the Intracellular Apicomplexan ParasiteToxoplasma gondii

Modulation of the Host Cell Proteome by the Intracellular Apicomplexan ParasiteToxoplasma gondii

Host cell manipulation by the human pathogen Toxoplasma gondii

Multinucleate host cells induced by Vittaforma corneae (Microsporidia)

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