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Gene expression profiles during subclinical Mycobacterium avium subspecies paratuberculosis infection in sheep can predict disease outcome
Paratuberculosis in ruminants is caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP) however exposure does not predetermine progression to clinical disease. The pathogenesis incorporates a subclinical phase during which MAP is capable of evading host immune responses throu...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547741/ https://www.ncbi.nlm.nih.gov/pubmed/31160677 http://dx.doi.org/10.1038/s41598-019-44670-w |
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author | Purdie, Auriol C. Plain, Karren M. Begg, Douglas J. de Silva, Kumudika Whittington, Richard J. |
author_facet | Purdie, Auriol C. Plain, Karren M. Begg, Douglas J. de Silva, Kumudika Whittington, Richard J. |
author_sort | Purdie, Auriol C. |
collection | PubMed |
description | Paratuberculosis in ruminants is caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP) however exposure does not predetermine progression to clinical disease. The pathogenesis incorporates a subclinical phase during which MAP is capable of evading host immune responses through adaptation of host cellular immune mechanisms. Presented are results of transcriptomic analysis of Merino sheep experimentally exposed to MAP and repeatedly sampled over the subclinical phase, identifying genes consistently changed over time in comparison to unexposed controls and associated with different disease outcomes. MAP exposed sheep were classified as diseased 45% (n = 9) or resilient 55% (n = 11). Significant gene expression changes were identified in the white blood cells of paucibacillary (n = 116), multibacillary (n = 98) and resilient cohorts (n = 53) compared to controls. Members of several gene families were differentially regulated, including S100 calcium binding, lysozyme function, MHC class I and class II, T cell receptor and transcription factors. The microarray findings were validated by qPCR. These differentially regulated genes are presented as putative biomarkers of MAP exposure, or of the specified disease or resilience outcomes. Further, in silico functional analysis of genes suggests that experimental MAP exposure in Merino sheep results in adaptations to cellular growth, proliferation and lipid metabolism. |
format | Online Article Text |
id | pubmed-6547741 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65477412019-06-10 Gene expression profiles during subclinical Mycobacterium avium subspecies paratuberculosis infection in sheep can predict disease outcome Purdie, Auriol C. Plain, Karren M. Begg, Douglas J. de Silva, Kumudika Whittington, Richard J. Sci Rep Article Paratuberculosis in ruminants is caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP) however exposure does not predetermine progression to clinical disease. The pathogenesis incorporates a subclinical phase during which MAP is capable of evading host immune responses through adaptation of host cellular immune mechanisms. Presented are results of transcriptomic analysis of Merino sheep experimentally exposed to MAP and repeatedly sampled over the subclinical phase, identifying genes consistently changed over time in comparison to unexposed controls and associated with different disease outcomes. MAP exposed sheep were classified as diseased 45% (n = 9) or resilient 55% (n = 11). Significant gene expression changes were identified in the white blood cells of paucibacillary (n = 116), multibacillary (n = 98) and resilient cohorts (n = 53) compared to controls. Members of several gene families were differentially regulated, including S100 calcium binding, lysozyme function, MHC class I and class II, T cell receptor and transcription factors. The microarray findings were validated by qPCR. These differentially regulated genes are presented as putative biomarkers of MAP exposure, or of the specified disease or resilience outcomes. Further, in silico functional analysis of genes suggests that experimental MAP exposure in Merino sheep results in adaptations to cellular growth, proliferation and lipid metabolism. Nature Publishing Group UK 2019-06-03 /pmc/articles/PMC6547741/ /pubmed/31160677 http://dx.doi.org/10.1038/s41598-019-44670-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Purdie, Auriol C. Plain, Karren M. Begg, Douglas J. de Silva, Kumudika Whittington, Richard J. Gene expression profiles during subclinical Mycobacterium avium subspecies paratuberculosis infection in sheep can predict disease outcome |
title | Gene expression profiles during subclinical Mycobacterium avium subspecies paratuberculosis infection in sheep can predict disease outcome |
title_full | Gene expression profiles during subclinical Mycobacterium avium subspecies paratuberculosis infection in sheep can predict disease outcome |
title_fullStr | Gene expression profiles during subclinical Mycobacterium avium subspecies paratuberculosis infection in sheep can predict disease outcome |
title_full_unstemmed | Gene expression profiles during subclinical Mycobacterium avium subspecies paratuberculosis infection in sheep can predict disease outcome |
title_short | Gene expression profiles during subclinical Mycobacterium avium subspecies paratuberculosis infection in sheep can predict disease outcome |
title_sort | gene expression profiles during subclinical mycobacterium avium subspecies paratuberculosis infection in sheep can predict disease outcome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547741/ https://www.ncbi.nlm.nih.gov/pubmed/31160677 http://dx.doi.org/10.1038/s41598-019-44670-w |
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