<i>In vitro</i>maturation of<i>Toxoplasma gondii</i>bradyzoites in human myotubes and their metabolomic characterization

Christiansen, Céline; Maus, Deborah; Melerowicz, Florian; Scholz, Jana; Murillo-León, Mateo; Steinfeldt, Tobias; Hoffmann, Tobias; Seeber, Frank; Blume, Martin

doi:10.1101/2021.01.15.426845

Cited by 5 publications

(1 citation statement)

References 99 publications

(168 reference statements)

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“…simplicity to produce the starting material of a 24-well plate can be used to infect two mice) also offers the possibility to test the infectiousness by oral gavage of parasite mutants. Interestingly, similar results were obtained using a human myotube-based in vitro culture model [54], indicating that in vitro production of infectious cysts is also possible in other cell types for a tropism exists in vivo.…”

Section: Discussionsupporting

confidence: 72%

Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology

et al. 2021

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Toxoplasma gondii is a eukaryotic parasite that forms latent cysts in the brain of immunocompetent individuals. The latent parasite infection of the immune-privileged central nervous system is linked to most complications. With no drug currently available to eliminate the latent cysts in the brain of infected hosts, the consequences of neurons' long-term infection are unknown. It has long been known that T. gondii specifically differentiates into a latent form (bradyzoite) in neurons, but how the infected neuron responds to the infection remains to be elucidated. We have established a new in vitro model resulting in the production of mature bradyzoite cysts in brain cells. Using dual, host and parasite RNA-seq, we characterized the dynamics of differentiation of the parasite, revealing the involvement of key pathways in this process. Moreover, we identified how the infected brain cells responded to the parasite infection revealing the drastic changes that take place. We showed that neuronal-specific pathways are strongly affected, with synapse signalling being particularly affected, especially glutamatergic synapse signalling. The establishment of this new in vitro model allows investigating both the dynamics of parasite differentiation and the specific response of neurons to long-term infection by this parasite.

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Section: Discussionsupporting

confidence: 72%

Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology

et al. 2021

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The pathogenicity and virulence of Toxoplasma gondii

Sanchez

Besteiro

2021

Virulence

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Toxoplasma gondii is a parasitic protist infecting a wide group of warm-blooded animals, ranging from birds to humans. While this infection is usually asymptomatic in healthy individuals, it can also lead to severe ocular or neurological outcomes in immunocompromised individuals or in developing fetuses. This obligate intracellular parasite has the ability to infect a considerable range of nucleated cells and can propagate in the intermediate host. Yet, under the pressure of the immune system it transforms into an encysted persistent form residing primarily in the brain and muscle tissues. Encysted parasites, which are resistant to current medication, may reactivate and give rise to an acute infection. The clinical outcome of toxoplasmosis depends on a complex balance between the host immune response and parasite virulence factors. Susceptibility to the disease is thus determined by both parasite strains and host species. Recent advances on our understanding of host cell-parasite interactions and parasite virulence have brought new insights into the pathophysiology of T. gondii infection and are summarized here.

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Primary brain cell infection byToxoplasma gondiireveals the extent and dynamics of parasite differentiation and its impact on neuron biology

Mouveaux

Roger

Gueye

et al. 2021

Preprint

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Toxoplasma gondii is a eukaryotic parasite that form latent cyst in the brain of immunocompetent individuals. The latent parasites infection of the immune privileged central nervous system is linked to most complications. With no drug currently available to eliminate the latent cysts in the brain of infected hosts, the consequences of neurons long-term infection are unknown. It has long been known that T. gondii specifically differentiate into a latent form (bradyzoite) in neurons, but how the infected neuron is responding to the infection remain to be elucidated. We have established a new in vitro model resulting in the production of fully mature bradyzoites cysts in brain cells. Using dual, host and parasite, RNA-seq we characterized the dynamics of differentiation of the parasite, revealing the involvement of key pathways in this process. Moreover, we identified how the infected brain cells responded to the parasite infection revealing the drastic changes that take place. We showed that neuronal specific pathways are strongly affected, with synapse signaling being particularly affected, especially glutamatergic synapse. The establishment of this new in vitro model allows to investigate both the dynamics of the parasite differentiation and the specific response of neurons to the long term infection by this parasite.

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In vitromaturation ofToxoplasma gondiibradyzoites in human myotubes and their metabolomic characterization

Cited by 5 publications

References 99 publications

Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology

Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology

The pathogenicity and virulence of Toxoplasma gondii

Primary brain cell infection byToxoplasma gondiireveals the extent and dynamics of parasite differentiation and its impact on neuron biology

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