Bovine extracellular vesicle LC-MSMS C4PR_LIV

The tick-borne protozoan parasites, Theileria annulata and T. parva are unique amongst intracellular eukaryotic pathogens because of their ability to induce a phenotype akin to transformation of the host cell. Infection with T. annulata, the causative agent of tropical theileriosis, is frequently fatal, via a cycle of neoplastic growth and tissue dissemination. Infected leukocytes become highly metastatic, forming foci of infected cells in multiple organs with subsequent destruction and disorganisation of the lymphoid system. Studies on extracellular vesicles (EV) have revealed that inter-cellular communication is critical for metastatic progression in cancer, and that the release of exosomes, a sub-set of EV, from tumour cells into the micro-environment induces pre-metastatic niche formation. Here we compared EV from a bovine lymphosarcoma cell line (BL20) and the same line infected in vitro with T. annulata (TBL20) by comparative mass spectrometry and miRNA profiling. Ingenuity Pathway Analysis revealed that many infection-associated proteins essential to migration and extracellular matrix digestion were up-regulated in EV from TBL20 cells compared with those from BL20 controls. Analysis of EV-associated miRNA revealed an altered repertoire of six host miRNA, each with a known role in tumour and/or infection biology. Focusing on bta-miR-181a and bta-miR-181b, we identified relevant mRNA targets and confirmed the interaction of bta-miR181a with intracellular adhesion molecule 1 (ICAM1). These data support a role for EV and their miRNA cargo in the pathobiology of Theileria infection.