title: Key Hub and Bottleneck Genes Differentiate the Macrophage Response to Virulent and Attenuated Mycobacterium bovis.
abstract: Mycobacterium bovis is an intracellular pathogen that causes tuberculosis in cattle. Following infection, the pathogen resides and persists inside host macrophages by subverting host immune responses via a diverse range of mechanisms. Here, a high-density bovine microarray platform was used to examine the bovine monocyte-derived macrophage transcriptome response to M. bovis infection relative to infection with the attenuated vaccine strain, M. bovis Bacille Calmette-Guérin. Differentially expressed genes were identified (adjusted P-value ≤0.01) and interaction networks generated across an infection time course of 2, 6, and 24 h. The largest number of biological interactions was observed in the 24-h network, which exhibited scale-free network properties. The 24-h network featured a small number of key hub and bottleneck gene nodes, including IKBKE, MYC, NFKB1, and EGR1 that differentiated the macrophage response to virulent and attenuated M. bovis strains, possibly via the modulation of host cell death mechanisms. These hub and bottleneck genes represent possible targets for immuno-modulation of host macrophages by virulent mycobacterial species that enable their survival within a hostile environment.
authors.affiliation: Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin , Dublin , Ireland ; Systems Biology Ireland, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Dublin , Ireland.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Killick
authors.affiliation: Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin , Dublin , Ireland.
authors.forename: David A
authors.initials: DA
authors.lastname: Magee
authors.affiliation: Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin , Dublin , Ireland ; IdentiGEN Ltd. , Dublin , Ireland.
authors.forename: Stephen D E
authors.initials: SD
authors.lastname: Park
authors.affiliation: Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin , Dublin , Ireland ; Biological Agents Unit, Health and Safety Executive , Leeds , UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Taraktsoglou
authors.affiliation: Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin , Dublin , Ireland.
authors.forename: John A
authors.initials: JA
authors.lastname: Browne
authors.affiliation: UCD School of Veterinary Medicine, University College Dublin , Dublin , Ireland ; Science Foundation Ireland (SFI) , Dublin , Ireland.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Conlon
authors.affiliation: Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin , Dublin , Ireland.
authors.forename: Nicolas C
authors.initials: NC
authors.lastname: Nalpas
authors.affiliation: Tuberculosis Diagnostics and Immunology Research Centre, UCD School of Veterinary Medicine, University College Dublin , Dublin , Ireland.
authors.forename: Eamonn
authors.initials: E
authors.lastname: Gormley
authors.affiliation: UCD School of Veterinary Medicine, University College Dublin , Dublin , Ireland ; UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Dublin , Ireland.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Gordon
authors.affiliation: Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin , Dublin , Ireland ; UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Dublin , Ireland.
authors.forename: David E
authors.initials: DE
authors.lastname: MacHugh
authors.affiliation: Smurfit Institute of Genetics, Trinity College , Dublin , Ireland.
authors.forename: Karsten
authors.initials: K
authors.lastname: Hokamp
keywords: BCG; Mycobacterium bovis; cattle; gene interaction network; macrophage; network; tuberculosis