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

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...

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Autores principales: Larcombe, Stephen D., Capewell, Paul, Jensen, Kirsty, Weir, William, Kinnaird, Jane, Glass, Elizabeth J., Shiels, Brian R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782480/
https://www.ncbi.nlm.nih.gov/pubmed/35061738
http://dx.doi.org/10.1371/journal.pone.0262051
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author Larcombe, Stephen D.
Capewell, Paul
Jensen, Kirsty
Weir, William
Kinnaird, Jane
Glass, Elizabeth J.
Shiels, Brian R.
author_facet Larcombe, Stephen D.
Capewell, Paul
Jensen, Kirsty
Weir, William
Kinnaird, Jane
Glass, Elizabeth J.
Shiels, Brian R.
author_sort Larcombe, Stephen D.
collection PubMed
description 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.
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spelling pubmed-87824802022-01-22 Susceptibility to disease (tropical theileriosis) is associated with differential expression of host genes that possess motifs recognised by a pathogen DNA binding protein Larcombe, Stephen D. Capewell, Paul Jensen, Kirsty Weir, William Kinnaird, Jane Glass, Elizabeth J. Shiels, Brian R. PLoS One Research Article 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. Public Library of Science 2022-01-21 /pmc/articles/PMC8782480/ /pubmed/35061738 http://dx.doi.org/10.1371/journal.pone.0262051 Text en © 2022 Larcombe et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Larcombe, Stephen D.
Capewell, Paul
Jensen, Kirsty
Weir, William
Kinnaird, Jane
Glass, Elizabeth J.
Shiels, Brian R.
Susceptibility to disease (tropical theileriosis) is associated with differential expression of host genes that possess motifs recognised by a pathogen DNA binding protein
title Susceptibility to disease (tropical theileriosis) is associated with differential expression of host genes that possess motifs recognised by a pathogen DNA binding protein
title_full Susceptibility to disease (tropical theileriosis) is associated with differential expression of host genes that possess motifs recognised by a pathogen DNA binding protein
title_fullStr Susceptibility to disease (tropical theileriosis) is associated with differential expression of host genes that possess motifs recognised by a pathogen DNA binding protein
title_full_unstemmed Susceptibility to disease (tropical theileriosis) is associated with differential expression of host genes that possess motifs recognised by a pathogen DNA binding protein
title_short Susceptibility to disease (tropical theileriosis) is associated with differential expression of host genes that possess motifs recognised by a pathogen DNA binding protein
title_sort susceptibility to disease (tropical theileriosis) is associated with differential expression of host genes that possess motifs recognised by a pathogen dna binding protein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782480/
https://www.ncbi.nlm.nih.gov/pubmed/35061738
http://dx.doi.org/10.1371/journal.pone.0262051
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