AUTHOR=Killick Kate E. , Magee David A. , Park Stephen D. E. , Taraktsoglou Maria , Browne John A. , Conlon Kevin M. , Nalpas Nicolas C. , Gormley Eamonn , Gordon Stephen V. , MacHugh David E. , Hokamp Karsten 

TITLE=Key Hub and Bottleneck Genes Differentiate the Macrophage Response to Virulent and Attenuated Mycobacterium bovis

JOURNAL=Frontiers in Immunology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2014.00422

DOI=10.3389/fimmu.2014.00422

ISSN=1664-3224

ABSTRACT=<p><italic>Mycobacterium bovis</italic> 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 <italic>M. bovis</italic> infection relative to infection with the attenuated vaccine strain, <italic>M. bovis</italic> Bacille Calmette–Guérin. Differentially expressed genes were identified (adjusted <italic>P</italic>-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 <italic>IKBKE, MYC, NFKB1</italic>, and <italic>EGR1</italic> that differentiated the macrophage response to virulent and attenuated <italic>M. bovis</italic> 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.</p>