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Immunological Response to Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex: An RNA-Sequence Analysis of the Bronchial Lymph Node Transcriptome.

Tizioto PC, Kim J, Seabury CM, Schnabel RD, Gershwin LJ, Van Eenennaam AL, Toaff-Rosenstein R, Neibergs HL, Bovine Respiratory Disease Complex Coordinated Agricultural Project Research TeamTaylor JF - PLoS ONE (2015)

Bottom Line: Dairy and beef cattle losses from BRD are profound worldwide and genetic studies have now been initiated to elucidate host loci which underlie susceptibility with the objective of enabling molecular breeding to reduce disease prevalence.We found that 142 differentially expressed genes were located in previously described quantitative trait locus regions associated with risk of BRD.However, we also found pathogen-specific expression profiles which suggest that host genetic variation for BRD susceptibility is pathogen dependent.

View Article: PubMed Central - PubMed

Affiliation: Embrapa Southeast Livestock, São Carlos, São Paulo, Brazil; Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America.

ABSTRACT
Susceptibility to bovine respiratory disease (BRD) is multi-factorial and is influenced by stress in conjunction with infection by both bacterial and viral pathogens. While vaccination is broadly used in an effort to prevent BRD, it is far from being fully protective and cases diagnosed from a combination of observed clinical signs without any attempt at identifying the causal pathogens are usually treated with antibiotics. Dairy and beef cattle losses from BRD are profound worldwide and genetic studies have now been initiated to elucidate host loci which underlie susceptibility with the objective of enabling molecular breeding to reduce disease prevalence. In this study, we employed RNA sequencing to examine the bronchial lymph node transcriptomes of controls and beef cattle which had individually been experimentally challenged with bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Pasteurella multocida, Mannheimia haemolytica or Mycoplasma bovis to identify the genes that are involved in the bovine immune response to infection. We found that 142 differentially expressed genes were located in previously described quantitative trait locus regions associated with risk of BRD. Mutations affecting the expression or amino acid composition of these genes may affect disease susceptibility and could be incorporated into molecular breeding programs. Genes involved in innate immunity were generally found to be differentially expressed between the control and pathogen-challenged animals suggesting that variation in these genes may lead to a heritability of susceptibility that is pathogen independent. However, we also found pathogen-specific expression profiles which suggest that host genetic variation for BRD susceptibility is pathogen dependent.

No MeSH data available.


Related in: MedlinePlus

Heatmap showing the Jensen–Shannon (JS) divergence between challenge groups estimated from FPKM values for all genes.
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pone.0131459.g002: Heatmap showing the Jensen–Shannon (JS) divergence between challenge groups estimated from FPKM values for all genes.

Mentions: To evaluate data quality, we first performed an analysis in which pairwise comparisons were made between all animals challenged with bacteria vs controls, all animals challenged with viruses vs control and all animals challenged with bacteria vs all animals challenged with viruses. The Cuffdiff output was also examined for reliability using several quality control methods. First, the variation between biological replicates was assessed using an MDS plot based on all expressed genes, which revealed a strong clustering of samples from control, bacterially and virally challenged animals with little variation between replicates (Fig 1). The first dimension clearly separated the virus- from the bacteria-challenged and control animals, while the second dimension separated controls from bacteria- and virus-challenged animals and suggests an ordering of pathogenicity. This postulate was also supported by the Jensen–Shannon divergence statistics between the challenged groups estimated from FPKM values for all genes (Fig 2) and by the principal component analysis (PC1 vs PC2; Fig 3), which show that the perturbation of gene expression was greatest for the animals challenged with viruses. The dynamic range of FPKM values was also evaluated by creating a boxplot of log10 transformed FPKM values for each biological replicate (Fig 4). The median FPKM values across the challenge groups were similar and the ranges indicate that our depth of sequence coverage was sufficient to allow the identification of genes with low transcript abundance.


Immunological Response to Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex: An RNA-Sequence Analysis of the Bronchial Lymph Node Transcriptome.

Tizioto PC, Kim J, Seabury CM, Schnabel RD, Gershwin LJ, Van Eenennaam AL, Toaff-Rosenstein R, Neibergs HL, Bovine Respiratory Disease Complex Coordinated Agricultural Project Research TeamTaylor JF - PLoS ONE (2015)

Heatmap showing the Jensen–Shannon (JS) divergence between challenge groups estimated from FPKM values for all genes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4484807&req=5

pone.0131459.g002: Heatmap showing the Jensen–Shannon (JS) divergence between challenge groups estimated from FPKM values for all genes.
Mentions: To evaluate data quality, we first performed an analysis in which pairwise comparisons were made between all animals challenged with bacteria vs controls, all animals challenged with viruses vs control and all animals challenged with bacteria vs all animals challenged with viruses. The Cuffdiff output was also examined for reliability using several quality control methods. First, the variation between biological replicates was assessed using an MDS plot based on all expressed genes, which revealed a strong clustering of samples from control, bacterially and virally challenged animals with little variation between replicates (Fig 1). The first dimension clearly separated the virus- from the bacteria-challenged and control animals, while the second dimension separated controls from bacteria- and virus-challenged animals and suggests an ordering of pathogenicity. This postulate was also supported by the Jensen–Shannon divergence statistics between the challenged groups estimated from FPKM values for all genes (Fig 2) and by the principal component analysis (PC1 vs PC2; Fig 3), which show that the perturbation of gene expression was greatest for the animals challenged with viruses. The dynamic range of FPKM values was also evaluated by creating a boxplot of log10 transformed FPKM values for each biological replicate (Fig 4). The median FPKM values across the challenge groups were similar and the ranges indicate that our depth of sequence coverage was sufficient to allow the identification of genes with low transcript abundance.

Bottom Line: Dairy and beef cattle losses from BRD are profound worldwide and genetic studies have now been initiated to elucidate host loci which underlie susceptibility with the objective of enabling molecular breeding to reduce disease prevalence.We found that 142 differentially expressed genes were located in previously described quantitative trait locus regions associated with risk of BRD.However, we also found pathogen-specific expression profiles which suggest that host genetic variation for BRD susceptibility is pathogen dependent.

View Article: PubMed Central - PubMed

Affiliation: Embrapa Southeast Livestock, São Carlos, São Paulo, Brazil; Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America.

ABSTRACT
Susceptibility to bovine respiratory disease (BRD) is multi-factorial and is influenced by stress in conjunction with infection by both bacterial and viral pathogens. While vaccination is broadly used in an effort to prevent BRD, it is far from being fully protective and cases diagnosed from a combination of observed clinical signs without any attempt at identifying the causal pathogens are usually treated with antibiotics. Dairy and beef cattle losses from BRD are profound worldwide and genetic studies have now been initiated to elucidate host loci which underlie susceptibility with the objective of enabling molecular breeding to reduce disease prevalence. In this study, we employed RNA sequencing to examine the bronchial lymph node transcriptomes of controls and beef cattle which had individually been experimentally challenged with bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Pasteurella multocida, Mannheimia haemolytica or Mycoplasma bovis to identify the genes that are involved in the bovine immune response to infection. We found that 142 differentially expressed genes were located in previously described quantitative trait locus regions associated with risk of BRD. Mutations affecting the expression or amino acid composition of these genes may affect disease susceptibility and could be incorporated into molecular breeding programs. Genes involved in innate immunity were generally found to be differentially expressed between the control and pathogen-challenged animals suggesting that variation in these genes may lead to a heritability of susceptibility that is pathogen independent. However, we also found pathogen-specific expression profiles which suggest that host genetic variation for BRD susceptibility is pathogen dependent.

No MeSH data available.


Related in: MedlinePlus