Authors

Discussion

The protozoan parasite, Theileria annulata is the causative agent of tropical theileriosis, a disease of cattle that is often severe and can be fatal. One of the most interesting features of the T. annulata infection cycle is its phase of neoplastic growth with similarity to cancer progression. In vivo, infected leukocytes become highly metastatic, and subsequent disorganisation and destruction of the lymphoid system occurs. As evidence from cancer biology has shown, metastasis is a highly complex process and although the pathogenic events have been defined, the mechanisms that initiate and drive metastasis are still largely unresolved. The study of extracellular vesicles (EV) has revealed that intercellular communication is critical for metastatic progression, and that the release of exosomes from tumour cells into the micro-environment induces pre-metastatic niche formation. It is intriguing to consider that exosomes derived from T. annulata infected cells may transfer proteins, soluble factors, mRNA, and microRNAs (miRNAs) to recipient cells and therefore may be involved in altering adaptive immune responses or have a role in migration and invasion of infected cells. To investigate the role of EV in this system we carried out mass spectrometry and miRNA profiling on EV from a bovine lymphosarcoma cell line (BL20) and the same cells infected with T. annulata (TBL20). The results demonstrate a very different protein profile in EV from TBL20 cells. Differentially regulated proteins were analysed using Ingenuity Pathway Analysis, revealing that many infection associated proteins and molecules shown to be essential for migration and extracellular matrix digestion in other systems are also up-regulated in TBL20 cells.miRNA sequencing of EV revealed a dysregulated repertoire of six miRNA, each with a known role in tumour biology. EV transfer experiments are underway to define the role of infe