RNA sequencing provides exquisite insight into the manipulation of the alveolar macrophage by tubercle bacilli.
Mycobacterium bovis, the agent of bovine tuberculosis, causes an estimated $3 billion annual losses to global agriculture due, in part, to the limitations of current diagnostics. Development of next-generation diagnostics requires a greater understanding of the interaction between the pathogen and the bovine host. Therefore, to explore the early response of the alveolar macrophage to infection, we report the first application of RNA-sequencing to define, in exquisite detail, the transcriptomes of M. bovis-infected and non-infected alveolar macrophages from ten calves at 2, 6, 24 and 48 hours post-infection. Differentially expressed sense genes were detected at these time points that revealed enrichment of innate immune signalling functions, and transcriptional suppression of host defence mechanisms (e.g., lysosome maturation). We also detected differentially expressed natural antisense transcripts, which may play a role in subverting innate immune mechanisms following infection. Furthermore, we report differential expression of novel bovine genes, some of which have immune-related functions based on orthology with human proteins. This is the first in-depth transcriptomics investigation of the alveolar macrophage response to the early stages of M. bovis infection and reveals complex patterns of gene expression and regulation that underlie the immunomodulatory mechanisms used by M. bovis to evade host defence mechanisms.
Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.
Nicolas C
NC
Nalpas
Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.
David A
DA
Magee
UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Kevin M
KM
Conlon
Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.
John A
JA
Browne
UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Claire
C
Healy
Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.
Kirsten E
KE
McLoughlin
Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.|UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Kévin
K
Rue-Albrecht
Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.
Paul A
PA
McGettigan
Systems Biology Ireland, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland.
Kate E
KE
Killick
Tuberculosis Diagnostics and Immunology Research Centre, UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Eamonn
E
Gormley
UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.|UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.|UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland.|UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland.
Stephen V
SV
Gordon
Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.|UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland.
David E
DE
MacHugh
D000818:Animals; D002415:Cats; D002417:Cattle; D019295:Computational Biology / Q000379:methods; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000276:immunology; D008247:Lysosomes / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D008297:Male; D058977:Molecular Sequence Annotation; D009163:Mycobacterium bovis / Q000276:immunology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction; D059467:Transcriptome; D014380:Tuberculosis, Bovine / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology
D018160:Receptors, Cytoplasmic and Nuclear; D053487:DEAD-box RNA Helicases