Cell type- and species-specific host responses to Toxoplasma gondii and its near relatives

Wong, Zhee Sheen; Borrelli, Sarah L. Sokol; Coyne, Carolyn; Boyle, Jon P.

doi:10.1016/j.ijpara.2020.05.001

Cited by 5 publications

(3 citation statements)

References 128 publications

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“…To our best knowledge, available data on T. gondii -driven host cell cycle modulation currently refer to haplotype I tachyzoites (RH strain) and indicate that this clonal lineage might control host cell cycle progression to ease its intracellular asexual development ( Brunet et al, 2008 ; Molestina et al, 2008 ; Velásquez et al, 2019 ; Wong et al, 2020 ; Pierre-Louis et al, 2022 ). Since several typical and atypical clonal lineages of T. gondii occur worldwide and show variable pathogenicity ( Dardé et al, 2014 ; Miller et al, 2023 ), we aimed to compare recent RH data (haplotype I) ( Velásquez et al, 2019 ) with haplotypes II and III (Me49 and NED, respectively) by infecting the same host cell type.…”

Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii Me49 and NED strains arrest host cell cycle progression and alter chromosome segregation in a strain-independent manner

Rojas-Barón,

Hermosilla,

Taubert

et al. 2024

Front. Microbiol.

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Toxoplasma gondii is an obligate intracellular parasite that modulates a broad range of host cell functions to guarantee its intracellular development and replication. T. gondii includes three classical clonal lineages exhibiting different degrees of virulence. Regarding the genetic diversity of T. gondii circulating in Europe, type II strains and, to a lesser extent, type III strains are the dominant populations, both in humans and animals. Infections with the type I strain led to widespread parasite dissemination and death in mice, while type III is considered avirulent. Previously, we demonstrated that primary endothelial cells infected with the T. gondii RH strain (haplotype I) were arrested in the G2/M-phase transition, triggering cytokinesis failure and chromosome missegregation. Since T. gondii haplotypes differ in their virulence, we here studied whether T. gondii-driven host cell cycle perturbation is strain-dependent. Primary endothelial cells were infected with T. gondii Me49 (type II strain) or NED (type III strain), and their growth kinetics were compared up to cell lysis (6–30 h p. i.). In this study, only slight differences in the onset of full proliferation were observed, and developmental data in principle matched those of the RH strain. FACS-based DNA quantification to estimate cell proportions experiencing different cell cycle phases (G0/1-, S-, and G2/M-phase) revealed that Me49 and NED strains both arrested the host cell cycle in the S-phase. Cyclins A2 and B1 as key molecules of S- and M-phase were not changed by Me49 infection, while NED infection induced cyclin B1 upregulation. To analyze parasite-driven alterations during mitosis, we demonstrated that both Me49 and NED infections led to impaired host cellular chromosome segregation and irregular centriole overduplication. Moreover, in line with the RH strain, both strains boosted the proportion of binucleated cells within infected endothelial cell layers, thereby indicating enhanced cytokinesis failure. Taken together, we demonstrate that all parasite-driven host cell cycle arrest, chromosome missegregation, and binucleated phenotypes are T. gondii-specific but strain independent.

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Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii Me49 and NED strains arrest host cell cycle progression and alter chromosome segregation in a strain-independent manner

Rojas-Barón,

Hermosilla,

Taubert

et al. 2024

Front. Microbiol.

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“…host-species dependent (reviewed in Hakimi et al, 2017;Lima and Lodoen, 2019;Poncet et al, 2019;Zhu et al, 2019;Wong et al, 2020).…”

Section: Srs52a Mic1 (T Sz) Mic2-m2ap (T B Sz) Got1 Family Proteinmentioning

confidence: 99%

Key Limitations and New Insights Into the Toxoplasma gondii Parasite Stage Switching for Future Vaccine Development in Human, Livestock, and Cats

Mévélec

Lakhrif

Dimier‐Poisson

2020

Front. Cell. Infect. Microbiol.

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Toxoplasmosis is a parasitic disease affecting human, livestock and cat. Prophylactic strategies would be ideal to prevent infection. In a One Health vaccination approach, the objectives would be the prevention of congenital disease in both women and livestock, prevention/reduction of T. gondii tissue cysts in food-producing animals; and oocyst shedding in cats. Over the last few years, an explosion of strategies for vaccine development, especially due to the development of genetic-engineering technologies has emerged. The field of vaccinology has been exploring safer vaccines by the generation of recombinant immunogenic proteins, naked DNA vaccines, and viral/bacterial recombinants vectors. These strategies based on single- or few antigens, are less efficacious than recombinant live-attenuated, mostly tachyzoite T. gondii vaccine candidates. Reflections on the development of an anti-Toxoplasma vaccine must focus not only on the appropriate route of administration, capable of inducing efficient immune response, but also on the choice of the antigen (s) of interest and the associated delivery systems. To answer these questions, the choice of the animal model is essential. If mice helped in understanding the protection mechanisms, the data obtained cannot be directly transposed to humans, livestock and cats. Moreover, effectiveness vaccines should elicit strong and protective humoral and cellular immune responses at both local and systemic levels against the different stages of the parasite. Finally, challenge protocols should use the oral route, major natural route of infection, either by feeding tissue cysts or oocysts from different T. gondii strains. Effective Toxoplasma vaccines depend on our understanding of the (1) protective host immune response during T. gondii invasion and infection in the different hosts, (2) manipulation and modulation of host immune response to ensure survival of the parasites able to evade and subvert host immunity, (3) molecular mechanisms that define specific stage development. This review presents an overview of the key limitations for the development of an effective vaccine and highlights the contributions made by recent studies on the mechanisms behind stage switching to offer interesting perspectives for vaccine development.

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“…It is one of the main causes of reproductive failure and is responsible for important economic losses in the ovine industry [ 1 , 2 ]. As an obligate intracellular parasite, T. gondii can infect any kind of nucleated cell, including muscle, nervous, epithelial or immune cells, where it multiplies via endodyogeny [ 3 , 4 ]. Macrophages (MØs) are the primary target cells of T. gondii and play a key role in the host’s immune response against it.…”

Section: Introductionmentioning

confidence: 99%

Effects of Ovine Monocyte-Derived Macrophage Infection by Recently Isolated Toxoplasma gondii Strains Showing Different Phenotypic Traits

Vallejo

Benavides

Arteche-Villasol

et al. 2022

Animals

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Ovine toxoplasmosis is one the most relevant reproductive diseases in sheep. The genetic variability among different Toxoplasma gondii isolates is known to be related to different degrees of virulence in mice and humans, but little is known regarding its potential effects in sheep. The aim of this study was to investigate the effect of genetic variability (types II (ToxoDB #1 and #3) and III (#2)) of six recently isolated strains that showed different phenotypic traits both in a normalized mouse model and in ovine trophoblasts, in ovine monocyte-derived macrophages and the subsequent transcript expression of cytokines and iNOS (inducible nitric oxide synthase). The type III isolate (TgShSp24) showed the highest rate of internalization, followed by the type II clonal isolate (TgShSp2), while the type II PRU isolates (TgShSp1, TgShSp3, TgShSp11 and TgShSp16) showed the lowest rates. The type II PRU strains, isolated from abortions, exhibited higher levels of anti-inflammatory cytokines and iNOS than those obtained from the myocardium of chronically infected sheep (type II PRU strains and type III), which had higher levels of pro-inflammatory cytokines. The present results show the existence of significant intra- and inter-genotypic differences in the parasite-macrophage relationship that need to be confirmed in in vivo experiments.

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Cell type- and species-specific host responses to Toxoplasma gondii and its near relatives

Cited by 5 publications

References 128 publications

Toxoplasma gondii Me49 and NED strains arrest host cell cycle progression and alter chromosome segregation in a strain-independent manner

Toxoplasma gondii Me49 and NED strains arrest host cell cycle progression and alter chromosome segregation in a strain-independent manner

Key Limitations and New Insights Into the Toxoplasma gondii Parasite Stage Switching for Future Vaccine Development in Human, Livestock, and Cats

Effects of Ovine Monocyte-Derived Macrophage Infection by Recently Isolated Toxoplasma gondii Strains Showing Different Phenotypic Traits

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