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

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 exami...

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Published in:Frontiers in immunology Vol. 5; p. 422
Main Authors: 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
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 01.10.2014
Subjects:
BCG
Cattle
Immunology
macrophage
Mycobacterium bovis
network
Tuberculosis
Mycobacterium bovis
BCG
tuberculosis
macrophage
cattle
gene interaction network
network
ISSN:1664-3224, 1664-3224
Online Access:Get full text
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Summary: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.
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Edited by: Kieran G. Meade, Teagasc, Ireland
This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology.
Reviewed by: Geanncarlo Lugo-Villarino, Centre National de la Recherche Scientifique, France; Silvia Bulfone-Paus, University of Manchester, UK; Graham Stewart, University of Surrey, UK
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2014.00422