Abstract
Theileria annulata is a tick-transmitted apicomplexan parasite that infects and transforms bovine leukocytes into disseminating tumors that cause a disease called tropical theileriosis. Using RNA sequencing we identified bovine genes, whose transcription is perturbed during Theileria-induced transformation to define the transcriptional atlas of transformed virulent versus attenuated (dampened dissemination) macrophages and transformed B cells. Dataset comparisons highlighted a small set of novel genes associated with Theileria-transformed leukocyte dissemination and the roles of Granzyme A (GZMA) and RAS guanyl-releasing protein 1 (RASGRP1) confirmed by CRISPR/Cas9-mediated down-regulation of their expression. Knockdown of both GZMA and RASGRP1 in attenuated macrophages led to a regain in their dissemination in Rag2/γC mice confirming in vivo both GZMA and RASGRP1 as novel dissemination suppressors.
Footnotes
↵* Co-first authors;
↵o Co-second authors
Financial Support: This study was supported by the Competitive Research Grant 4 (OSR-2015-CRG4-2610) from the Office for Sponsored Research in King Abdullah University of Science and Technology (KAUST). ST was supported by a ParaFrap postdoctoral fellowship and GL acknowledges support from Labex ParaFrap (ANR-11-LABX-0024), INSERM and the CNRS.