Journal
OPEN BIOLOGY
Volume 11, Issue 10, Pages -Publisher
ROYAL SOC
DOI: 10.1098/rsob.210053
Keywords
brain cell; Toxoplasma gondii; neuron; differentiation; bradyzoites; parasite
Categories
Funding
- Centre National de la Recherche Scientifique (CNRS)
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- CPER CTRL Longevite
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Toxoplasma gondii is a eukaryotic parasite that forms latent cysts in the brain, leading to compromised immune-privileged central nervous system and affected neuronal pathways. Using a new in vitro model, researchers studied the dynamics of parasite differentiation and neuronal response to long-term infection, revealing significant changes in synaptic signaling pathways, particularly glutamatergic synapse signaling.
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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