High-resolution transcriptomics of bovine purified protein derivative-stimulated peripheral blood from cattle infected with Mycobacterium bovis across an experimental time course. (September 2022)

• Record Type: Journal Article
• Authors: Correia, Carolina N.; McHugo, Gillian P.; Browne, John A.; McLoughlin, Kirsten E.; Nalpas, Nicolas C.; Magee, David A.; Whelan, Adam O.; Villarreal-Ramos, Bernardo; Vordermeier, H. Martin; Gormley, Eamonn; Gordon, Stephen V.; MacHugh, David E.
• Is Part Of: Tuberculosis. Volume 136(2022)
• Publication Date: 2022-09
• Subjects: Biomarker -- Blood -- Bovine tuberculosis -- Diagnostics -- Mycobacterium bovis -- Transcriptomics; 616.995
• DOI: 10.1016/j.tube.2022.102235
• Languages: English
• ISSNs: 1472-9792

Abstract

Abstract: Objectives: Improved bovine tuberculosis (bTB) diagnostics with higher sensitivity and specificity are urgently required. A better understanding of the peripheral blood transcriptional response of Mycobacterium bovis -infected animals after bovine purified protein derivative (PPD-b) stimulation of whole blood—an important component of current bTB diagnostics—will provide new information for development of better diagnostics. Methods: RNA sequencing (RNA-seq) was used to study the peripheral blood transcriptome after stimulation with PPD-b across four time points (−1 wk pre-infection, and +1 wk, +2 wk, and +10 wk post-infection) from a 14-week M. bovis infection time course experiment with ten age-matched Holstein-Friesian cattle. Results: In vitro PPD-b stimulation of peripheral blood from M. bovis -infected and non-infected cattle elicited a strong transcriptional response. Comparison of PPD-b stimulated, and unstimulated samples revealed higher expression of genes encoding cytokine receptors, transcription factors, and interferon-inducible proteins. Lower expression was seen for genes encoding proteins involved in antimicrobial activity, C-type lectin receptors, inhibition of signal transduction, and genes encoding metal ion transporters. Conclusions: A transcriptional signature associated with the peripheral blood response to PPD-b stimulation consisting of 170 genes was identified exclusively in the post-infection time points. Therefore, this represents a panel of potential biomarkers of M. bovis infection.