Abstract
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.
Highlights
Toxoplasma gondii is a unicellular eukaryotic pathogen
To characterize the T. gondii spontaneous differentiation dynamics in this in vitro model, we followed the expression of tachyzoite (TgSAG1) and bradyzoite (Cyst wall labelled by Dolichos bifluorus lectin and p21, a late bradyzoite marker [39]) markers over time
Spontaneous differentiation occurred within a short time frame in the brain cells with the appearance of parasites expressing a marker of the cyst wall 24 h after infection representing more than 90% of the parasite population after 96 h
Summary
Toxoplasma gondii is a unicellular eukaryotic pathogen. It belongs to the Apicomplexa phylum, which encompasses some of the deadliest pathogens of medical and veterinary importance, including Plasmodium (the cause of malaria), Cryptosporidium (responsible for cryptosporidiosis) and Eimeria (causative agent of coccidiosis). Toxoplasma gondii is an obligate intracellular parasite. Toxoplasmosis is generally asymptomatic, it can lead to the development of focal central nervous system (CNS) infections in immunocompromised hosts. Toxoplasma is a clinically important opportunistic pathogen that can cause birth defects in the offspring of newly infected mothers. The worldwide seroprevalence of T. gondii infection is estimated to be between 30% and 70% in humans, it differs significantly depending on geographical areas [1]
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