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      Transcriptome analysis of immune genes in peripheral blood mononuclear cells of young foals and adult horses

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          Abstract

          During the neonatal period, the ability to generate immune effector and memory responses to vaccines or pathogens is often questioned. This study was undertaken to obtain a global view of the natural differences in the expression of immune genes early in life. Our hypothesis was that transcriptome analyses of peripheral blood mononuclear cells (PBMCs) of foals (on day 1 and day 42 after birth) and adult horses would show differential gene expression profiles that characterize natural immune processes. Gene ontology enrichment analysis provided assessment of biological processes affected by age, and a list of 897 genes with ≥2 fold higher (p<0.01) expression in day 42 when compared to day 1 foal samples. Up-regulated genes included B cell and T cell receptor diversity genes; DNA replication enzymes; natural killer cell receptors; granzyme B and perforin; complement receptors; immunomodulatory receptors; cell adhesion molecules; and cytokines/chemokines and their receptors. The list of 1,383 genes that had higher (p<0.01) expression on day 1 when compared to day 42 foal samples was populated by genes with roles in innate immunity such as antimicrobial proteins; pathogen recognition receptors; cytokines/chemokines and their receptors; cell adhesion molecules; co-stimulatory molecules; and T cell receptor delta chain. Within the 742 genes with increased expression between day 42 foal and adult samples, B cell immunity was the main biological process (p = 2.4E-04). Novel data on markedly low (p<0.0001) TLR3 gene expression, and high (p≤0.01) expression of IL27, IL13RA1, IREM-1, SIRL-1, and SIRPα on day 1 compared to day 42 foal samples point out potential mechanisms of increased susceptibility to pathogens in early life. The results portray a progression from innate immune gene expression predominance early in life to adaptive immune gene expression increasing with age with a putative overlay of immune suppressing genes in the neonatal phase. These results provide insight to the unique attributes of the equine neonatal and young immune system, and offer many avenues of future investigation.

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          Most cited references106

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          edgeR: a Bioconductor package for differential expression analysis of digital gene expression data

          Summary: It is expected that emerging digital gene expression (DGE) technologies will overtake microarray technologies in the near future for many functional genomics applications. One of the fundamental data analysis tasks, especially for gene expression studies, involves determining whether there is evidence that counts for a transcript or exon are significantly different across experimental conditions. edgeR is a Bioconductor software package for examining differential expression of replicated count data. An overdispersed Poisson model is used to account for both biological and technical variability. Empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference. The methodology can be used even with the most minimal levels of replication, provided at least one phenotype or experimental condition is replicated. The software may have other applications beyond sequencing data, such as proteome peptide count data. Availability: The package is freely available under the LGPL licence from the Bioconductor web site (http://bioconductor.org). Contact: mrobinson@wehi.edu.au
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            Genome sequence, comparative analysis, and population genetics of the domestic horse.

            We report a high-quality draft sequence of the genome of the horse (Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.
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              Functional significance of the perforin/granzyme cell death pathway.

              Perforin/granzyme-induced apoptosis is the main pathway used by cytotoxic lymphocytes to eliminate virus-infected or transformed cells. Studies in gene-disrupted mice indicate that perforin is vital for cytotoxic effector function; it has an indispensable, but undefined, role in granzyme-mediated apoptosis. Despite its vital importance, the molecular and cellular functions of perforin and the basis of perforin and granzyme synergy remain poorly understood. The purpose of this review is to evaluate critically recent findings on cytotoxic granule-mediated cell death and to assess the functional significance of postulated cell-death pathways in appropriate pathophysiological contexts, including virus infection and susceptibility to experimental or spontaneous tumorigenesis.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: MethodologyRole: SoftwareRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: MethodologyRole: SoftwareRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                5 September 2018
                2018
                : 13
                : 9
                : e0202646
                Affiliations
                [1 ] Equine Immunology Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States of America
                [2 ] Cornell Bioinformatics Facility, Cornell University, Ithaca, NY, United States of America
                University of Queensland, AUSTRALIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-6440-5272
                Article
                PONE-D-17-43102
                10.1371/journal.pone.0202646
                6124769
                30183726
                6c299de3-f65c-4896-9a67-26ab92016738
                © 2018 Tallmadge et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 8 December 2017
                : 7 August 2018
                Page count
                Figures: 10, Tables: 5, Pages: 28
                Funding
                Funded by: USDA-National Institute of Food and Agriculture
                Award ID: 2011-02923
                Award Recipient :
                This study was funded by the United States Department of Agriculture National Institute of Food and Agriculture, grant number 2011-02923 (MJBF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Genetics
                Gene Expression
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Equines
                Horses
                Biology and Life Sciences
                Immunology
                Immune System Proteins
                Immune Receptors
                T Cell Receptors
                Medicine and Health Sciences
                Immunology
                Immune System Proteins
                Immune Receptors
                T Cell Receptors
                Biology and Life Sciences
                Biochemistry
                Proteins
                Immune System Proteins
                Immune Receptors
                T Cell Receptors
                Biology and Life Sciences
                Cell Biology
                Signal Transduction
                Immune Receptors
                T Cell Receptors
                Biology and Life Sciences
                Biochemistry
                Proteins
                T Cell Receptors
                Biology and Life Sciences
                Computational Biology
                Genome Analysis
                Transcriptome Analysis
                Biology and Life Sciences
                Genetics
                Genomics
                Genome Analysis
                Transcriptome Analysis
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Immune Cells
                Antibody-Producing Cells
                B Cells
                Biology and Life Sciences
                Immunology
                Immune Cells
                Antibody-Producing Cells
                B Cells
                Medicine and Health Sciences
                Immunology
                Immune Cells
                Antibody-Producing Cells
                B Cells
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Blood Cells
                White Blood Cells
                B Cells
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Immune Cells
                White Blood Cells
                B Cells
                Biology and Life Sciences
                Immunology
                Immune Cells
                White Blood Cells
                B Cells
                Medicine and Health Sciences
                Immunology
                Immune Cells
                White Blood Cells
                B Cells
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Blood Cells
                White Blood Cells
                T Cells
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Immune Cells
                White Blood Cells
                T Cells
                Biology and Life Sciences
                Immunology
                Immune Cells
                White Blood Cells
                T Cells
                Medicine and Health Sciences
                Immunology
                Immune Cells
                White Blood Cells
                T Cells
                Biology and Life Sciences
                Immunology
                Immune System
                Medicine and Health Sciences
                Immunology
                Immune System
                Biology and Life Sciences
                Immunology
                Immune System Proteins
                Immune Receptors
                Toll-like Receptors
                Medicine and Health Sciences
                Immunology
                Immune System Proteins
                Immune Receptors
                Toll-like Receptors
                Biology and Life Sciences
                Biochemistry
                Proteins
                Immune System Proteins
                Immune Receptors
                Toll-like Receptors
                Biology and Life Sciences
                Cell Biology
                Signal Transduction
                Immune Receptors
                Toll-like Receptors
                Custom metadata
                The transcriptome data is available at the NCBI Gene Expression Omnibus under the accession number GSE101117.

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