<i>Theileria</i> secretes proteins to subvert its host leukocyte

Tajeri, Shahin; Langsley, Gordon

doi:10.1111/boc.202000096

Cited by 16 publications

(21 citation statements)

References 64 publications

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“…Several Theileria effector proteins, defined as proteins of transformative Theileria species which are translocated into the host cell or integrated into the schizont membrane and interact with host proteins, have been described in recent years (reviewed in Tajeri and Langsley, 2021). Some proteins have been shown to translocate to the host cell nucleus, and key examples are three Tash family proteins TashAT2 (TA20095), TashHN (TA20090) and SuAT1 (TA03135) (Swan et al, 1999;Swan et al, 2001;Swan et al, 2003;Shiels et al, 2004).…”

Section: Secretion Of Theileria-encoded Effector Proteins Into Host Cell Compartmentsmentioning

confidence: 99%

Theileria’s Strategies and Effector Mechanisms for Host Cell Transformation: From Invasion to Immortalization

Woods

Perry

Brühlmann

et al. 2021

Front. Cell Dev. Biol.

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One of the first events that follows invasion of leukocytes by Theileria sporozoites is the destruction of the surrounding host cell membrane and the rapid association of the intracellular parasite with host microtubules. This is essential for the parasite to establish its niche within the cytoplasm of the invaded leukocyte and sets Theileria spp. apart from other members of the apicomplexan phylum such as Toxoplasma gondii and Plasmodium spp., which reside within the confines of a host-derived parasitophorous vacuole. After establishing infection, transforming Theileria species (T. annulata, T. parva) significantly rewire the signaling pathways of their bovine host cell, causing continual proliferation and resistance to ligand-induced apoptosis, and conferring invasive properties on the parasitized cell. Having transformed its target cell, Theileria hijacks the mitotic machinery to ensure its persistence in the cytoplasm of the dividing cell. Some of the parasite and bovine proteins involved in parasite-microtubule interactions have been fairly well characterized, and the schizont expresses at least two proteins on its membrane that contain conserved microtubule binding motifs. Theileria-encoded proteins have been shown to be translocated to the host cell cytoplasm and nucleus where they have the potential to directly modify signaling pathways and host gene expression. However, little is known about their mode of action, and even less about how these proteins are secreted by the parasite and trafficked to their target location. In this review we explore the strategies employed by Theileria to transform leukocytes, from sporozoite invasion until immortalization of the host cell has been established. We discuss the recent description of nuclear pore-like complexes that accumulate on membranes close to the schizont surface. Finally, we consider putative mechanisms of protein and nutrient exchange that might occur between the parasite and the host. We focus in particular on differences and similarities with recent discoveries in T. gondii and Plasmodium species.

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Section: Secretion Of Theileria-encoded Effector Proteins Into Host Cell Compartmentsmentioning

confidence: 99%

Theileria’s Strategies and Effector Mechanisms for Host Cell Transformation: From Invasion to Immortalization

Woods

Perry

Brühlmann

et al. 2021

Front. Cell Dev. Biol.

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“…First and foremost, is the ability of the intracellular schizont to transform host myeloid cells and B lymphocytes 7 . Through secretion of a repertoire of proteins on to the parasite surface or translocated into the host cell compartment, the schizont fine tunes host cell signalling pathways to create an infected leukocyte with cancer-like properties 8 . T. annulata -transformed leukocytes have high dissemination potential and secrete a range of proteases and inflammatory cytokines that influence their pathogenicity 9 .…”

Section: Introductionmentioning

confidence: 99%

Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion

Tajeri

Momeux

Saintpierre

et al. 2022

Sci Rep

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A fungal metabolite, FR235222, specifically inhibits a histone deacetylase of the apicomplexan parasite Toxoplasma gondii and TgHDAC3 has emerged as a key factor regulating developmental stage transition in this species. Here, we exploited FR235222 to ask if changes in histone acetylation regulate developmental stage transition of Theileria annulata, another apicomplexan species. We found that FR235222 treatment of T. annulata-infected transformed leukocytes induced a proliferation arrest. The blockade in proliferation was due to drug-induced conversion of intracellular schizonts to merozoites that lack the ability to maintain host leukocyte cell division. Induction of merogony by FR235222 leads to an increase in expression of merozoite-marker (rhoptry) proteins. RNA-seq of FR235222-treated T. annulata-infected B cells identified deregulated expression of 468 parasite genes including a number encoding parasite ApiAP2 transcription factors. Thus, similar to T. gondii, FR235222 inhibits T. annulata HDAC (TaHDAC1) activity and places parasite histone acetylation as a major regulatory event of the transition from schizonts to merozoites.

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Section: Introductionmentioning

confidence: 99%

Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion

Tajeri

Momeux

Saintpierre

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

A fungal metabolite, FR235222, specifically inhibits a histone deacetylase of the apicomplexan parasite Toxoplasma gondii and TgHDAC3 has emerged as a key factor regulating developmental stage transition in this species. Here, we exploited FR235222 to ask if changes in histone acetylation regulate developmental stage transition of Theileria annulata another apicomplexan species. We found that FR235222 treatment of T. annulata-infected transformed leukocytes induced a proliferation arrest. The blockade in proliferation was due to drug-induced conversion of intracellular schizonts to merozoites that lack the ability to maintain host leukocyte cell division. Induction of merogony by FR235222 leads to an increase in expression of merozoite-marker (rhoptry) proteins. RNA-seq of FR235222-treated T. annulata-infected B cells identified deregulated expression of 468 parasite genes, which included a number encoding parasite ApiAP2 transcription factors. Thus, similar to T. gondii, FR235222 inhibits T. annulata HDAC (TaHDAC1) activity and places parasite histone acetylation as a major regulatory event of the transition from schizonts to merozoites and hence pathogenesis of tropical theileriosis.

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Theileria secretes proteins to subvert its host leukocyte

Cited by 16 publications

References 64 publications

Theileria’s Strategies and Effector Mechanisms for Host Cell Transformation: From Invasion to Immortalization

Theileria’s Strategies and Effector Mechanisms for Host Cell Transformation: From Invasion to Immortalization

Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion

Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion

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