MicroRNA profiling of the bovine alveolar macrophage response to Mycobacterium bovis infection suggests pathogen survival is enhanced by microRNA regulation of endocytosis and lysosome trafficking

Mycobacterium bovis, the causative agent of bovine tuberculosis, a major problem for global agriculture, spreads via an airborne route and is taken up by alveolar macrophages (AM) in the lung. Here, we describe the first next-generation sequencing (RNA-seq) approach to temporally profile miRNA expre...

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Bibliographic Details
Published in:Tuberculosis (Edinburgh, Scotland) Vol. 95; no. 1; pp. 60 - 67
Main Authors: Vegh, Peter, Magee, David A., Nalpas, Nicolas C., Bryan, Kenneth, McCabe, Matthew S., Browne, John A., Conlon, Kevin M., Gordon, Stephen V., Bradley, Daniel G., MacHugh, David E., Lynn, David J.
Format: Journal Article
Language:English
Published: Scotland Elsevier Ltd 01.01.2015
Subjects:
Alveolar macrophage
Animals
Bos taurus
Cattle
Cells, Cultured
Down-Regulation
Endocytosis - immunology
Gene Expression - genetics
Gene Expression - immunology
Gene Expression Profiling - methods
Immunity, Innate - immunology
Infectious Disease
Interleukin-1 Receptor-Associated Kinases - antagonists & inhibitors
Lysosomes - immunology
Macrophages, Alveolar - immunology
Male
microRNA
MicroRNAs - genetics
MicroRNAs - immunology
MicroRNAs - physiology
Mycobacterium bovis
Mycobacterium bovis - immunology
Pulmonary/Respiratory
Real-Time Polymerase Chain Reaction - methods
RNA, Bacterial - genetics
RNA, Bacterial - immunology
RNA-seq
Sequence Analysis, RNA - methods
Transfection - methods
Transforming Growth Factor beta2 - antagonists & inhibitors
Tuberculosis
Tuberculosis, Bovine - immunology
Tuberculosis, Pulmonary - immunology
Up-Regulation
microRNA
Tuberculosis
Bos taurus
RNA-seq
Mycobacterium bovis
Alveolar macrophage
ISSN:1472-9792, 1873-281X, 1873-281X
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Summary:Mycobacterium bovis, the causative agent of bovine tuberculosis, a major problem for global agriculture, spreads via an airborne route and is taken up by alveolar macrophages (AM) in the lung. Here, we describe the first next-generation sequencing (RNA-seq) approach to temporally profile miRNA expression in primary bovine AMs post-infection with M. bovis. One, six, and forty miRNAs were identified as significantly differentially expressed at 2, 24 and 48 h post-infection, respectively. The differential expression of three miRNAs (bta-miR-142-5p, bta-miR-146a, and bta-miR-423-3p) was confirmed by RT-qPCR. Pathway analysis of the predicted mRNA targets of differentially expressed miRNAs suggests that these miRNAs preferentially target several pathways that are functionally relevant for mycobacterial pathogenesis, including endocytosis and lysosome trafficking, IL-1 signalling and the TGF-β pathway. Over-expression studies using a bovine macrophage cell-line (Bomac) reveal the targeting of two key genes in the innate immune response to M. bovis, IL-1 receptor-associated kinase 1 (IRAK1) and TGF-β receptor 2 (TGFBR2), by miR-146. Taken together, our study suggests that miRNAs play a key role in tuning the complex interplay between M. bovis survival strategies and the host immune response.
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ISSN:1472-9792
1873-281X
1873-281X
DOI:10.1016/j.tube.2014.10.011