Abstract

Theileria annulata is an obligate intracellular protozoan parasite of the phylum Apicomplexa. Theileria sporozoites invade bovine leukocytes and develop into a multinucleate syncytial macroschizont that causes uncontrolled proliferation and dissemination of infected and transformed leukocytes. Activator protein 1 (AP-1) is a transcription factor driving expression of genes involved in proliferation and dissemination and is therefore a key player in Theileria-induced leukocytes transformation. Ta9 possesses a signal peptide allowing it to be secreted into the infected leukocyte cytosol and be presented to CD8 T cells in the context of MHC class I. First, we confirmed that Ta9 is secreted into the infected leukocyte cytosol, and then we generated truncated versions of GFP-tagged Ta9 and tested their ability to activate AP-1 in non-infected HEK293T human kidney embryo cells. The ability to activate AP-1-driven transcription was found to reside in the C-terminal 100 amino acids of Ta9 distant to the N-terminally located epitopes recognised by CD8+ T cells. Secreted Ta9 has therefore, not only the ability to stimulate CD8+ T cells, but also the potential to activate AP-1-driven transcription and contribute to T. annulata-induced leukocyte transformation.

Highlights

  • The protozoan parasite T. annulata is the causative agent of a tick-borne disease of cattle called tropical theileriosis that causes morbidity and loss of productivity in indigenous cattle, and a severe and often lethal disease in exotic and cross breed cattle in a wide geographic distribution ranging from the Mediterranean littoral regions of Europe and Africa to the Near and Middle East to India and China in Asia [1,2]

  • GFP-Ta9-1-335 reacted with the hyper-immune serum and the fusion protein was used to affinity purify specific anti-Ta9 antibodies (Fig 1B) that were used in indirect immunofluorescence assays (IFA) to confirm the reported presence of Ta9 in the infected leukocyte cytosol [17,18]

  • The host cell transcription factor Activator protein 1 (AP-1) has been demonstrated to play a role in the dissemination of transformed leukocytes infected with Theileria parasites, notably due to its capacity to drive transcription of the mmp9 gene [12,24,25,26]

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Summary

Introduction

The protozoan parasite T. annulata is the causative agent of a tick-borne disease of cattle called tropical theileriosis that causes morbidity and loss of productivity in indigenous cattle, and a severe and often lethal disease in exotic and cross breed cattle in a wide geographic distribution ranging from the Mediterranean littoral regions of Europe and Africa to the Near and Middle East to India and China in Asia [1,2]. T. annulata is transmitted by ticks of the genus Hyalomma and during feeding on cattle infected ticks inject sporozoites that infect B cells and macrophages rather than T cells [3,4]. Theileria annulata Ta9 protein and AP-1 activation data collection and analysis, decision to publish, or preparation of the manuscript

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