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bioRxiv · 10.1101/2022.04.19.488769

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

Correia, C. N.·McHugo, G. P.·Browne, J. A.·McLoughlin, K. E.·Nalpas, N. C.·Magee, D. A.·Whelan, A. O.·Villarreal-Ramos, B.·Vordermeier, H. M.·Gormley, E.·Gordon, S. V.·MacHugh, D. E.
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Abstract

ObjectivesImproved 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. MethodsRNA 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. ResultsIn 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. ConclusionsA 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.

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Correia, C. N., McHugo, G. P., Browne, J. A., McLoughlin, K. E., Nalpas, N. C., Magee, D. A., Whelan, A. O., Villarreal-Ramos, B., Vordermeier, H. M., Gormley, E., Gordon, S. V., MacHugh, D. E.. 2022-04-19. High-resolution transcriptomics of bovine purified protein derivative-stimulated peripheral blood from cattle infected with Mycobacterium bovis across an experimental time course. https://doi.org/10.1101/2022.04.19.488769

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