When a protozoan pathogen imitates cancer

A few specialized tick-transmitted protozoa cause fatal infectious diseases in cattle through a unique cell biological mechanism, the transformation of host leukocytes into cancer-like cells. These 'transformative' parasites, such as Theileria annulata, hijack host signaling pathways and, during the schizont stage of their complex life cycle, cause uncontrolled proliferation and immortalization of infected cells, likely through a broad repertoire of fine-tuned effector proteins. This review summarizes recent advancements on the parasite-host interactions proposed to underlie this remarkable transformation phenotype. Exported parasite protein families are significantly expanded in T. annulata and often exhibit intrinsically disordered protein regions as a consistent motif. We highlight current knowledge gaps and technical challenges, whose resolution promises a better understanding of parasite effector function. Expanding our understanding of this exceptional eukaryotic system could not only enhance strategies for controlling disease but also provide fundamental insights into cell and cancer biology.