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Deep sequencing of the uterine immune response to bacteria during the equine oestrous cycle

BACKGROUND: The steroid hormone environment in healthy horses seems to have a significant impact on the efficiency of their uterine immune response. The objective of this study was to characterize the changes in gene expression in the equine endometrium in response to the introduction of bacterial p...

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Autores principales: Marth, Christina D., Young, Neil D., Glenton, Lisa Y., Noden, Drew M., Browning, Glenn F., Krekeler, Natali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647707/
https://www.ncbi.nlm.nih.gov/pubmed/26572250
http://dx.doi.org/10.1186/s12864-015-2139-3
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author Marth, Christina D.
Young, Neil D.
Glenton, Lisa Y.
Noden, Drew M.
Browning, Glenn F.
Krekeler, Natali
author_facet Marth, Christina D.
Young, Neil D.
Glenton, Lisa Y.
Noden, Drew M.
Browning, Glenn F.
Krekeler, Natali
author_sort Marth, Christina D.
collection PubMed
description BACKGROUND: The steroid hormone environment in healthy horses seems to have a significant impact on the efficiency of their uterine immune response. The objective of this study was to characterize the changes in gene expression in the equine endometrium in response to the introduction of bacterial pathogens and the influence of steroid hormone concentrations on this expression. METHODS: Endometrial biopsies were collected from five horses before and 3 h after the inoculation of Escherichia coli once in oestrus (follicle >35 mm in diameter) and once in dioestrus (5 days after ovulation) and analysed using high-throughput RNA sequencing techniques (RNA-Seq). RESULTS: Comparison between time points revealed that 2422 genes were expressed at significantly higher levels and 2191 genes at significantly lower levels 3 h post inoculation in oestrus in comparison to pre-inoculation levels. In dioestrus, the expression of 1476 genes was up-regulated and 383 genes were down-regulated post inoculation. Many immune related genes were found to be up-regulated after the introduction of E. coli. These include pathogen recognition receptors, particularly toll-like receptors TLR2 and 4 and NOD-like receptor NLRC5. In addition, several interleukins including IL1B, IL6, IL8 and IL1ra were significantly up-regulated. Genes for chemokines, including CCL 2, CXCL 6, 9, 10, 11 and 16 and those for antimicrobial peptides, including secretory phospholipase sPLA(2), lipocalin 2, lysozyme and equine β-defensin 1, as well as the gene for tissue inhibitor for metalloproteinases TIMP-1 were also up-regulated post inoculation. CONCLUSION: The results of this study emphasize the complexity of an effective uterine immune response during acute endometritis and the tight balance between pro- and anti-inflammatory factors required for efficient elimination of bacteria. It is one of the first high-throughput analyses of the uterine inflammatory response in any species and several new potential targets for treatment of inflammatory diseases of the equine uterus have been identified. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2139-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-46477072015-11-18 Deep sequencing of the uterine immune response to bacteria during the equine oestrous cycle Marth, Christina D. Young, Neil D. Glenton, Lisa Y. Noden, Drew M. Browning, Glenn F. Krekeler, Natali BMC Genomics Research Article BACKGROUND: The steroid hormone environment in healthy horses seems to have a significant impact on the efficiency of their uterine immune response. The objective of this study was to characterize the changes in gene expression in the equine endometrium in response to the introduction of bacterial pathogens and the influence of steroid hormone concentrations on this expression. METHODS: Endometrial biopsies were collected from five horses before and 3 h after the inoculation of Escherichia coli once in oestrus (follicle >35 mm in diameter) and once in dioestrus (5 days after ovulation) and analysed using high-throughput RNA sequencing techniques (RNA-Seq). RESULTS: Comparison between time points revealed that 2422 genes were expressed at significantly higher levels and 2191 genes at significantly lower levels 3 h post inoculation in oestrus in comparison to pre-inoculation levels. In dioestrus, the expression of 1476 genes was up-regulated and 383 genes were down-regulated post inoculation. Many immune related genes were found to be up-regulated after the introduction of E. coli. These include pathogen recognition receptors, particularly toll-like receptors TLR2 and 4 and NOD-like receptor NLRC5. In addition, several interleukins including IL1B, IL6, IL8 and IL1ra were significantly up-regulated. Genes for chemokines, including CCL 2, CXCL 6, 9, 10, 11 and 16 and those for antimicrobial peptides, including secretory phospholipase sPLA(2), lipocalin 2, lysozyme and equine β-defensin 1, as well as the gene for tissue inhibitor for metalloproteinases TIMP-1 were also up-regulated post inoculation. CONCLUSION: The results of this study emphasize the complexity of an effective uterine immune response during acute endometritis and the tight balance between pro- and anti-inflammatory factors required for efficient elimination of bacteria. It is one of the first high-throughput analyses of the uterine inflammatory response in any species and several new potential targets for treatment of inflammatory diseases of the equine uterus have been identified. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2139-3) contains supplementary material, which is available to authorized users. BioMed Central 2015-11-14 /pmc/articles/PMC4647707/ /pubmed/26572250 http://dx.doi.org/10.1186/s12864-015-2139-3 Text en © Marth et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Marth, Christina D.
Young, Neil D.
Glenton, Lisa Y.
Noden, Drew M.
Browning, Glenn F.
Krekeler, Natali
Deep sequencing of the uterine immune response to bacteria during the equine oestrous cycle
title Deep sequencing of the uterine immune response to bacteria during the equine oestrous cycle
title_full Deep sequencing of the uterine immune response to bacteria during the equine oestrous cycle
title_fullStr Deep sequencing of the uterine immune response to bacteria during the equine oestrous cycle
title_full_unstemmed Deep sequencing of the uterine immune response to bacteria during the equine oestrous cycle
title_short Deep sequencing of the uterine immune response to bacteria during the equine oestrous cycle
title_sort deep sequencing of the uterine immune response to bacteria during the equine oestrous cycle
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647707/
https://www.ncbi.nlm.nih.gov/pubmed/26572250
http://dx.doi.org/10.1186/s12864-015-2139-3
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