Loss of predator aversion in female rats after Toxoplasma gondii infection is not dependent on ovarian steroids

Abdulai-Saiku, Samira; Vyas, Ajai

doi:10.1016/j.bbi.2017.04.005

Cited by 22 publications

(26 citation statements)

References 25 publications

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“…Similarly, severely impaired histone acetylation at IFN-γ-regulated promoters during infection, and a parasite-mediated defect in the recruitment of chromatin remodeling complexes have been reported [14,20]. Decreased promoter methylation, through DNA methyltransferase activity has been shown to increase gene expression of neurons in Toxoplasma-infected rats [21].…”

Section: Cellular and Molecular Life Sciencesmentioning

confidence: 94%

Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways

Sabou

Doderer-Lang

Leyer

et al. 2019

Cell. Mol. Life Sci.

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Toxoplasmosis, caused by the apicomplexan parasite Toxoplasma gondii, is one of the most common infections in the world due to the lifelong persistence of this parasite in a latent stage. This parasite hijacks host signaling pathways through epigenetic mechanisms which converge on key nuclear proteins. Here, we report a new parasite persistence strategy involving T. gondii rhoptry protein ROP16 secreted early during invasion, which targets the transcription factor UHRF1 (ubiquitinlike containing PHD and RING fingers domain 1), and leads to host cell cycle arrest. This is mediated by DNMT activity and chromatin remodeling at the cyclin B1 gene promoter through recruitment of phosphorylated UHRF1 associated with a repressive multienzymatic protein complex. This leads to deacetylation and methylation of histone H3 surrounding the cyclin B1 promoter to epigenetically silence its transcriptional activity. Moreover, T. gondii infection causes DNA hypermethylation in its host cell, by upregulation of DNMTs. ROP16 is already known to activate and phosphorylate protective immunity transcription factors such as STAT 3/6/5 and modulate host signaling pathways in a strain-dependent manner. Like in the case of STAT6, the strain-dependent effects of ROP16 on UHRF1 are dependent on a single amino-acid polymorphism in ROP16. This study demonstrates that Toxoplasma hijacks a new epigenetic initiator, UHRF1, through an early event initiated by the ROP16 parasite kinase.Keywords Toxoplasma gondii · UHFR1 · ROP16 · Cyclin B1 · DNMT · Epigenetic regulation Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Section: Cellular and Molecular Life Sciencesmentioning

confidence: 94%

Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways

Sabou

Doderer-Lang

Leyer

et al. 2019

Cell. Mol. Life Sci.

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“…These monoamines are also used by hosts to regulate a wide variety of brain functions from stress to reproduction (Libersat and Pflueger, 2004;Nelson and Trainor, 2007;Øverli et al, 2007). As discussed earlier, hormones such as testosterone are also thought to play a key role in neuropharmological manipulation (Auger et al, 2011;Hari Dass and Vyas, 2014;Abdulai-Saiku and Vyas, 2017).…”

Section: Neuropharmacological Host Manipulation Monoamines and Hormonesmentioning

confidence: 99%

“…Testosterone crosses the blood brain barrier in the infected host to have a wide variety of effects including hypomethylation of the arginine vasopressin gene within the posterodorsal medial amygdala resulting in elevated vasopressin expression that may alter behavior of male rats (Auger et al, 2011;Hari Dass and Vyas, 2014;Abdulai-Saiku and Vyas, 2017). Interestingly, testosterone has been implicated in acanthocephalan-gammarid host manipulation and other hostparasite systems as well (Klein, 2004;Lewis et al, 2016).…”

Section: Genomic Manipulationmentioning

confidence: 99%

“…This suggests that the epigenetic mechanism found in Toxoplasma may be present at a similar level in these other systems. However, failure to replicate the behavioral effects of testosterone in female hosts implies this mechanism of host manipulation struggles to account for the sexually dimorphic effects of testosterone (Lewis et al, 2016;Abdulai-Saiku and Vyas, 2017).…”

Section: Genomic Manipulationmentioning

confidence: 99%

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Lessons in Mind Control: Trends in Research on the Molecular Mechanisms behind Parasite-Host Behavioral Manipulation

Herbison

2017

Front. Ecol. Evol.

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Scientific and public interest in host manipulation by parasites has surged over the past few decades, resulting in an exponential growth of cases where potential behavioral manipulation has been identified. However, these studies dwarf the number of genuine attempts to elucidate the mechanistic processes behind this behavioral manipulation. Ultimately, this imbalance has slowed progress in the study of the mechanisms underlying host manipulation. As it stands, research suggests that the mechanisms of host manipulation fall into three categories: immunological, genomic/proteomic and neuropharmacological, and forth potential category: symbioant-mediated manipulation. After exploration of the literature pertaining to these four pathways, four major trends become evident. First and foremost, there is a severe disconnect between the observed molecular and behavioral shifts in a parasitized host. Indeed, very rarely a study demonstrates that molecular changes observed in a host are the result of active manipulation by the resident parasite, or that these molecular changes directly result in behavioral manipulation that increases the parasite's fitness. Secondly, parasites may often employ multiple pathways in unison to achieve control over their hosts. Despite this, current scientific approaches usually focus on each manipulation pathway in isolation rather than integrating them. Thirdly, the relative amount of host-parasite systems yet to be investigated in terms of molecular manipulation is staggering. Finally, as a result of the aforementioned trends, guiding mechanisms or principles for the multiple types of behavioral manipulation are yet to be found. Researchers should look to identify the manipulative factors required to generate the molecular changes seen in hosts, while also considering the "multi-pronged" approach parasites are taking to manipulate behavior. Assessing gene expression and its products during transitional periods in parasites may be a key methodological approach for tackling these recent trends in the host manipulation literature.

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“…The cause of this discrepancy cannot be ascertained with confidence. In fact, we have observed stress-induced anxiogenesis and the infection-induced loss of fear in the same animal facility and same animal strain before these experiments 1 , 5 – 7 , 13 . The only difference between the experimental circumstances has been a construction project that was ongoing during the present experiments.…”

Section: Discussionmentioning

confidence: 82%

Effects of stress or infection on rat behavior show robust reversals due to environmental disturbance

et al. 2018

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Background: The behavior of animals is intricately linked to the environment; a relationship that is often studied in laboratory conditions by using environmental perturbations to study biological mechanisms underlying the behavioral change. Methods: This study pertains to two such well-studied and well-replicated perturbations, i.e., stress-induced anxiogenesis and Toxoplasma gondii -induced loss of innate fear. Here, we demonstrate that behavioral outcomes of these experimental manipulations are contingent upon the ambient quality of the wider environment where animal facilities are situated. Results: During late 2014 and early 2015, a building construction project started adjacent to our animal facility. During this phase, we observed that maternal separation stress caused anxiolysis, rather than historically observed anxiogenesis, in laboratory rats. We also found that Toxoplasma gondii infection caused an increase, rather than historically observed decrease, in innate aversion to predator odors in rats. Conclusion: These observations suggest that effects of stress and Toxoplasma gondii are dependent on variables in the environment that often go unreported in the published literature.

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Loss of predator aversion in female rats after Toxoplasma gondii infection is not dependent on ovarian steroids

Cited by 22 publications

References 25 publications

Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways

Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways

Lessons in Mind Control: Trends in Research on the Molecular Mechanisms behind Parasite-Host Behavioral Manipulation

Effects of stress or infection on rat behavior show robust reversals due to environmental disturbance

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