Abstract
Bovine tuberculosis, caused by infection with Mycobacterium bovis, is a major endemic disease affecting cattle populations worldwide, despite the implementation of stringent surveillance and control programs in many countries. The development of high-throughput functional genomics technologies, including gene expression microarrays and RNA-sequencing (RNA-seq), has enabled detailed analysis of the host transcriptome to M. bovis infection, particularly at the macrophage and peripheral blood level. In the present study, we have analyzed the peripheral blood leukocyte (PBL) transcriptome of eight natural M. bovis-infected and eight age- and sex-matched non-infected control Holstein-Friesian animals using RNA-seq. In addition, we compared gene expression profiles generated using RNA-seq with those previously generated using the high-density Affymetrix® GeneChip® Bovine Genome Array platform from the same PBL-extracted RNA. A total of 3,250 differentially expressed (DE) annotated genes were detected in the M. bovis-infected samples relative to the controls (adjusted P-value ≤0.05), with the number of genes displaying decreased relative expression (1,671) exceeding those with increased relative expression (1,579). Ingenuity® Systems Pathway Analysis (IPA) of all DE genes revealed enrichment for genes with immune function. Notably, transcriptional suppression was observed among several of the top-ranking canonical pathways including Leukocyte Extravasation Signaling. Comparative platform analysis demonstrated that RNA-seq detected a larger number of annotated DE genes (3,250) relative to the microarray (1,398), of which 917 genes were common to both technologies and displayed the same direction of expression. Finally, we show that RNA-seq had an increased dynamic range compared to the microarray for estimating differential gene expression.
Highlights
Bovine tuberculosis (BTB) is caused by infection with Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex (MTC)
Further examination of the results showed that 917 DE Ensembl genes had the same direction of expression on both platforms; 2,331 DE Ensembl genes were unique to the RNA-seq results (i.e., DE using RNA-seq but not DE on the microarray platform); and 479 DE Ensembl genes were unique to the microarray (i.e., DE on the microarray platform but not DE on the RNA-seq platform)
The target tissue for studies of the host response has generally been peripheral blood collected from infected and noninfected individuals or animals; peripheral blood provides an accessible biological sample that reflects the host immunological and pathological changes induced at the site of infection [9]
Summary
Bovine tuberculosis (BTB) is caused by infection with Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex (MTC). Econometric analyses incorporating agricultural production and human health indices have placed BTB as the fourth most important disease of cattle, costing an estimated $3 billion on a global scale annually [2]. Evasion of host immune defenses enables the pathogen to survive and replicate within phagocytic macrophages, the primary innate immune cell that mediates the response to infection, and can result in dissemination of infection via the lymph system leading to disease progression and pathology [5]. The immune response to BTB is complex and is largely characterized by macrophage-mediated development of protective TH1-type responses following initial exposure to the pathogen. The progression of infection may be due to the modulation and suppression of specific immune mechanisms by the pathogen [5]
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