<i>Toxoplasma gondii</i> infection induces the formation of host’s nuclear granules containing poly(A)-binding proteins

Fischer, Karlee; Roberts, Mikayla; Roscoe, Scott; Avci, Yasin; Ananvoranich, Sirinart

doi:10.1139/cjm-2017-0755

Cited by 2 publications

(2 citation statements)

References 23 publications

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“…Translational control is also achieved via trans-regulatory factors, such as RNA-binding proteins, microRNAs, and "specialized ribosomes" (93)(94)(95). A recent study by Fischer and colleagues reported that infection by T. gondii causes the formation of stress granules containing poly(A)-binding proteins (PABPs) in the nucleus of the host cell (96). PABPs regulate several steps in mRNA processing, such as export, degradation, stability, polyadenylation, and deadenylation (97,98).…”

Section: Discussionmentioning

confidence: 99%

The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome

et al. 2018

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The intracellular parasite promotes infection by targeting multiple host cell processes; however, whether it modulates mRNA translation is currently unknown. Here, we show that infection of primary murine macrophages with type I or II strains causes a profound perturbation of the host cell translatome. Notably, translation of transcripts encoding proteins involved in metabolic activity and components of the translation machinery was activated upon infection. In contrast, the translational efficiency of mRNAs related to immune cell activation and cytoskeleton/cytoplasm organization was largely suppressed. Mechanistically, bolstered mechanistic target of rapamycin (mTOR) signaling to selectively activate the translation of mTOR-sensitive mRNAs, including those with a 5'-terminal oligopyrimidine (5' TOP) motif and those encoding mitochondrion-related proteins. Consistent with parasite modulation of host mTOR-sensitive translation to promote infection, inhibition of mTOR activity suppressed replication. Thus, selective reprogramming of host mRNA translation represents an important subversion strategy during infection.

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Section: Discussionmentioning

confidence: 99%

The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome

et al. 2018

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“…Poly-adenosine-binding proteins (PABPs) are RNA binding proteins that bind to polyadenylated RNA and are involved in metabolic pathways of the mRNA, and their sub-cellular distribution changes in response to cellular stress (Gray et al, 2015). Nuclear granulation of PABPs is induced in T. gondii -infected HFFs (Fischer et al, 2018), which may enable the parasite to influence the host cell transcriptome. Quantitative proteomic analysis of HFFs also indicates that T. gondii globally reprograms key metabolic pathways in the host cell, including glycolysis, lipid, and sterol metabolism, mitosis, apoptosis, and structural-protein expression (Nelson et al, 2008).…”

Section: Host Innate Immunity To T Gondii Infectionmentioning

confidence: 99%

Mechanisms of Human Innate Immune Evasion by Toxoplasma gondii

Lima

Lodoen

2019

Front. Cell. Infect. Microbiol.

118

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Toxoplasma gondii is an intracellular protozoan parasite of global importance that can remarkably infect, survive, and replicate in nearly all mammalian cells. Notably, 110 years after its discovery, Toxoplasmosis is still a neglected parasitic infection. Although most human infections with T. gondii are mild or asymptomatic, T. gondii infection can result in life-threatening disease in immunocompromised individuals and in the developing fetus due to congenital infection, underscoring the role of the host immune system in controlling the parasite. Recent evidence indicates that T. gondii elicits a robust innate immune response during infection. Interestingly, however, T. gondii has evolved strategies to successfully bypass or manipulate the immune system and establish a life-long infection in infected hosts. In particular, T. gondii manipulates host immunity through the control of host gene transcription and dysregulation of signaling pathways that result in modulation of cell adhesion and migration, secretion of immunoregulatory cytokines, production of microbicidal molecules, and apoptosis. Many of these host-pathogen interactions are governed by parasite effector proteins secreted from the apical secretory organelles, including the rhoptries and dense granules. Here, we review recent findings on mechanisms by which T. gondii evades host innate immunity, with a focus on parasite evasion of the human innate immune system.

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Toxoplasma gondii infection induces the formation of host’s nuclear granules containing poly(A)-binding proteins

Cited by 2 publications

References 23 publications

The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome

The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome

Mechanisms of Human Innate Immune Evasion by Toxoplasma gondii

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