Biology and epidemiology of<i>Toxoplasma gondii</i>in man and animals

Hill, Dolores E.; Sreekumar, C.; Dubey, J. P.

doi:10.1079/ahr2005100

Cited by 471 publications

(403 citation statements)

References 156 publications

(134 reference statements)

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“…A.H. is a guest editor invited by the EditorialBoard. 1 To whom correspondence may be addressed. E-mail: rwek@iupui.edu or wjsulliv@iupui.…”

Section: Resultsmentioning

confidence: 99%

“…Protozoa in the phylum Apicomplexa are parasites that require a eukaryotic host cell to replicate. Toxoplasma gondii is one such obligate intracellular parasite, capable of using virtually all warm-blooded vertebrates as host organisms (1). Acute Toxoplasma infection can cause spontaneous abortion or congenital birth defects, as well as severe disease in immunocompromised patients.…”

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confidence: 99%

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Phosphorylation of eukaryotic initiation factor-2α promotes the extracellular survival of obligate intracellular parasite Toxoplasma gondii

Joyce

Queener²,

Wek

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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While seeking a new host cell, obligate intracellular parasites, such as the protozoan Toxoplasma gondii, must be able to endure the stress of an extracellular environment. The mechanisms Toxoplasma use to remain viable while deprived of a host cell are not understood. We have previously shown that phosphorylation of Toxoplasma eukaryotic initiation factor-2α (TgIF2α) is a conserved response to stress. Here we report the characterization of Toxoplasma harboring a point mutation (S71A) in TgIF2α that prevents phosphorylation. Results show that TgIF2α phosphorylation is critical for parasite viability because the TgIF2α-S71A mutants are illequipped to cope with life outside the host cell. The TgIF2α-S71A mutants also showed a significant delay in producing acute toxoplasmosis in vivo. We conclude that the phosphorylation of TgIF2α plays a crucial role during the lytic cycle by ameliorating the stress of the extracellular environment while the parasite searches for a new host cell.Apicomplexa | toxoplasmosis | stress | translation control | eIF2

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“…A.H. is a guest editor invited by the EditorialBoard. 1 To whom correspondence may be addressed. E-mail: rwek@iupui.edu or wjsulliv@iupui.…”

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Phosphorylation of eukaryotic initiation factor-2α promotes the extracellular survival of obligate intracellular parasite Toxoplasma gondii

Joyce

Queener²,

Wek

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Toxoplasma gondii, the agent of toxoplasmosis and a major cause of AIDS-associated encephalitis, is a ubiquitous protozoan parasite that serves as a model organism for the study of host cell-parasite interaction (1)(2)(3)(4). T. gondii readily invades most mammalian cell types and proliferates within a parasitophorous vacuole (PV), 2 whose membrane combines host plasma membrane-and parasite-derived components (5).…”

mentioning

confidence: 99%

Coordinate Control of Host Centrosome Position, Organelle Distribution, and Migratory Response by Toxoplasma gondii via Host mTORC2

Wang

Weiss

Orlofsky

2010

Journal of Biological Chemistry

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The invasion of host cells by Toxoplasma gondii is accompanied by a reorganization of host cell structure, in which the host centrosome and Golgi apparatus are localized to the vacuole, and mitochondria, microtubules, and endolysosomes are recruited to the vacuole perimeter. The mechanism and functional significance of this process have not been well defined. Here, we report that the centrosome-vacuole association was abolished in mammalian target of rapamycin complex 2 (mTORC2)-deficient cells, which also displayed a disordered distribution of perivacuolar host mitochondria and lysosomes. Infection of fibroblasts led to stable, mTORC2-dependent activation of Akt, and Akt inhibition mimicked the effect of mTORC2 ablation on centrosome, mitochondria, and lysosome localization. Mobilization of the centrosome by Akt inhibition was abrogated by inhibitors of glycogen synthase kinase 3 (GSK3), implying that the centrosome is constrained to the vacuole through an mTORC2-Akt-GSK3 pathway. Infected cells were incapable of migration in a wounded monolayer model, and this effect was associated with the inability of centrosomes to reorient in the direction of migration. Both migration and centrosome reorientation were fully restored upon ablation of mTORC2. These findings provide the first linkage of host signals to parasite-mediated host cell reorganization and demonstrate migratory suppression as a novel functional consequence of this process that is associated with mTORC2-mediated centrosome constraint.Toxoplasma gondii, the agent of toxoplasmosis and a major cause of AIDS-associated encephalitis, is a ubiquitous protozoan parasite that serves as a model organism for the study of host cell-parasite interaction (1-4). T. gondii readily invades most mammalian cell types and proliferates within a parasitophorous vacuole (PV), 2 whose membrane combines host plasma membrane-and parasite-derived components (5). The PV provides an interface for interaction with the host and serves as a focal point for a remarkable reorganization of host cell architecture. The host centrosome and Golgi become closely associated with the PV, which is tightly wrapped by host microtubules, mitochondria, and endoplasmic reticulum. In addition, host endolysosomes and autophagosomes localize near the vacuole perimeter (6 -9). Mitochondria-PV association is dependent on a parasite secretory product, ROP2, and knockdown of ROP2 results in profound defects in Toxoplasma growth and virulence (10). Apart from ROP2, no host or parasite signal involved in the reorganization process has been identified. Furthermore, apart from mitochondria-PV association, the functional significance of the reorganized host cell architecture remains unknown.The orientation of the centrosome and Golgi is susceptible to regulation in mammalian cells, for example during directional responses to migratory stimuli (11-13). A potential mechanism, then, of parasite-mediated reorganization is the mimicry of host signals that govern the polarization response, resulting in a stable, in...

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“…[1][2][3] In the congenital toxoplasmosis model, the severity of infection appears to depend mainly on the gestational age at which the transmission took place, but also on the parasite load determined in amniotic fluid samples, and possibly on the parasite genotype and the genetic predisposition of the host. [3][4][5][6][7] All human diseases have genetic components, which can be decisive for the outcome of the disease, or be combined with environmental factors.…”

Section: Introductionmentioning

confidence: 99%

HLA-DQA1/B1 alleles as putative susceptibility markers in congenital toxoplasmosis

et al. 2016

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Host and parasite genotypes are among the factors associated with congenital toxoplasmosis pathogenesis. As HLA class II molecules play a key role in the immune system regulation, the aim of this study was to investigate whether HLA-DQA1/B1 alleles are associated with susceptibility or protection to congenital toxoplasmosis. One hundred and twenty-two fetuses with and 103 without toxoplasmosis were studied. The two study groups were comparable according to a number of socio-demographic and genetic variables. HLA alleles were typed by PCR-SSP. In the HLA-DQA1 region, the allele frequencies showed that Ã 01:03 and Ã 03:02 alleles could confer susceptibility (ORD 3.06, p D 0.0002 and ORD 9.60, pD 0.0001, respectively) as they were more frequent among infected fetuses. Regarding the HLA-DQB1 region, the Ã 05:04 allele could confer susceptibility (OR D 6.95, p < 0.0001). Of the 122 infected fetuses, 10 presented susceptibility haplotypes contrasting with only one in the non-infected group. This difference was not statistically significant after correction for multiple comparison (OR D 9.37, pD0.011). In the casuistic, there were two severely damaged fetuses with high parasite loads determined in amniotic fluid samples and HLA-DQA1 susceptibility alleles. In the present study, a discriminatory potential of HLA-DQA1/B1 alleles to identify susceptibility to congenital toxoplasmosis and the most severe cases has been shown.

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Biology and epidemiology ofToxoplasma gondiiin man and animals

Cited by 471 publications

References 156 publications

Phosphorylation of eukaryotic initiation factor-2α promotes the extracellular survival of obligate intracellular parasite Toxoplasma gondii

Phosphorylation of eukaryotic initiation factor-2α promotes the extracellular survival of obligate intracellular parasite Toxoplasma gondii

Coordinate Control of Host Centrosome Position, Organelle Distribution, and Migratory Response by Toxoplasma gondii via Host mTORC2

HLA-DQA1/B1 alleles as putative susceptibility markers in congenital toxoplasmosis

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