Susceptibility to disease (tropical theileriosis) is associated with differential expression of host genes that possess motifs recognised by a pathogen DNA binding protein

Larcombe, S. D., Capewell, P. , Jensen, K., Weir, W. , Kinnaird, J., Glass, E. J. and Shiels, B. R. (2022) Susceptibility to disease (tropical theileriosis) is associated with differential expression of host genes that possess motifs recognised by a pathogen DNA binding protein. PLoS ONE, 17(1), e0262051. (doi: 10.1371/journal.pone.0262051) (PMID:35061738) (PMCID:PMC8782480)

Abstract

Background: Knowledge of factors that influence the outcome of infection are crucial for determining the risk of severe disease and requires the characterisation of pathogen-host interactions that have evolved to confer variable susceptibility to infection. Cattle infected by Theileria annulata show a wide range in disease severity. Native (Bos indicus) Sahiwal cattle are tolerant to infection, whereas exotic (Bos taurus) Holstein cattle are susceptible to acute disease. Methodology/Principal findings: We used RNA-seq to assess whether Theileria infected cell lines from Sahiwal cattle display a different transcriptome profile compared to Holstein and screened for altered expression of parasite factors that could generate differences in host cell gene expression. Significant differences (<0.1 FDR) in the expression level of a large number (2211) of bovine genes were identified, with enrichment of genes associated with Type I IFN, cholesterol biosynthesis, oncogenesis and parasite infection. A screen for parasite factors found limited evidence for differential expression. However, the number and location of DNA motifs bound by the TashAT2 factor (TA20095) were found to differ between the genomes of B. indicus vs. B. taurus, and divergent motif patterns were identified in infection-associated genes differentially expressed between Sahiwal and Holstein infected cells. Conclusions/Significance: We conclude that divergent pathogen-host molecular interactions that influence chromatin architecture of the infected cell are a major determinant in the generation of gene expression differences linked to disease susceptibility.

• Item Type: Articles
• Additional Information: Funding: This work was funded by BBSRC: grant BB/L004739/1 and a BBSRC Strategic Programme grant (Control of Infectious Diseases: [BB/ P013740/1]).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Shiels, Professor Brian and Larcombe, Dr Stephen and Kinnaird, Dr Jane and Weir, Professor Willie and Capewell, Dr Paul
• Authors: Larcombe, S. D., Capewell, P., Jensen, K., Weir, W., Kinnaird, J., Glass, E. J., and Shiels, B. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright: © 2022 Larcombe et al.
• First Published: First published in PLoS ONE 17(1): e0262051
• Publisher Policy: Reproduced under a Creative Commons licence

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
190742		Control of tick borne disease: molecular epidemiology, host resistance and novel vaccine antigens	Brian Shiels	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/L004739/1	Institute of Biodiversity, Animal Health and Comparative Medicine