Comparative transcriptional analysis identifies genes associated with the attenuation of Theileria parva infected cells after long-term in vitro culture

Administration of attenuated autologous Theileria parva infected cells can be used as an alternative to the infection-and-treatment method for inducing immunological protection against East Coast Fever. The mechanism of attenuation however has not been described. Using RNA sequencing, the transcriptomes of both host and parasite in uninfected (control), pathogenic (day 7 post-infection) and attenuated (day 69 post-infection) T. parva infected bovine CD4+ T-cells were characterized and compared. Our findings suggest that three major mechanisms are associated with attenuation of T. parva-infected cells – a decrease in proliferation, a partial restoration of the inflammatory profile, and a shift in metabolism. Several host genes (TRAIL, PD-1, TGF-ß and granzymes) were identified as candidates for further exploration. Evaluation of the parasite transcriptomes in these cells also provided first insights into potential candidate T. parva genes involved in attenuation, but subsequent studies are required to further examine these. Overall design: To investigate the mechanisms of attenuation Theileria parva infected bovine CD4 T-cell lines were established. RNA seq was then performed on cell lines from 6 animals at 3 time points (day 0 (uninfected), day 7 (pathogenic) and day 69 (attenuated). 2 cell lines could not be maintained in vitro until day 69 as such there are only 4 samples for day 69).