The secreted Theileria annulata Ta9 protein contributes to activation of the AP-1 transcription factor

• Published in: PloS one 2018-05, Vol.13 (5), p.e0196875-e0196875
• Main Authors: Unlu, Ahmet Hakan, Tajeri, Shahin, Bilgic, Huseyin Bilgin, Eren, Hasan, Karagenc, Tulin, Langsley, Gordon
• Format: Article
• Language: English
• Subjects: Activator protein 1; Amino acids; Animals; Biology and Life Sciences; Bovidae; Cattle; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Proliferation - genetics; Cytosol; Embryo cells; Epitopes; Epitopes - immunology; Gene expression; Gene Expression Regulation - genetics; Gene Expression Regulation - immunology; Genetic aspects; Genetic transformation; HEK293 Cells; Host-Parasite Interactions - genetics; Host-Parasite Interactions - immunology; Humans; Leukocytes; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Medicine and Health Sciences; Parasites; Protein Sorting Signals - genetics; Protozoa; Protozoan Infections, Animal - genetics; Protozoan Infections, Animal - immunology; Protozoan Infections, Animal - parasitology; Protozoan Proteins - genetics; Sporozoites; T-Lymphocytes - immunology; Theileria; Theileria annulata; Theileria annulata - genetics; Theileria annulata - pathogenicity; Transcription activation; Transcription Factor AP-1 - genetics; Transcription factors; Transformation; White blood cells
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0196875

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.