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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Veröffentlicht in:Frontiers in immunology Jg. 5; S. 422
Hauptverfasser: 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
Sprache:Englisch
Veröffentlicht: Switzerland Frontiers Media S.A 01.10.2014
Schlagworte:
BCG
Cattle
Immunology
macrophage
Mycobacterium bovis
network
Tuberculosis
Mycobacterium bovis
BCG
tuberculosis
macrophage
cattle
gene interaction network
network
ISSN:1664-3224, 1664-3224
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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.
AbstractList 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.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.
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 immunomodulation of host macrophages by virulent mycobacterial species that enable their survival within a hostile environment.
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.
Author MacHugh, David E.
Park, Stephen D. E.
Hokamp, Karsten
Conlon, Kevin M.
Gordon, Stephen V.
Magee, David A.
Taraktsoglou, Maria
Browne, John A.
Nalpas, Nicolas C.
Gormley, Eamonn
Killick, Kate E.
AuthorAffiliation 8 UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Dublin , Ireland
7 Tuberculosis Diagnostics and Immunology Research Centre, UCD School of Veterinary Medicine, University College Dublin , Dublin , Ireland
4 Biological Agents Unit, Health and Safety Executive , Leeds , UK
5 UCD School of Veterinary Medicine, University College Dublin , Dublin , Ireland
3 IdentiGEN Ltd. , Dublin , Ireland
1 Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin , Dublin , Ireland
2 Systems Biology Ireland, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Dublin , Ireland
6 Science Foundation Ireland (SFI) , Dublin , Ireland
9 Smurfit Institute of Genetics, Trinity College , Dublin , Ireland
AuthorAffiliation_xml – name: 4 Biological Agents Unit, Health and Safety Executive , Leeds , UK
– name: 2 Systems Biology Ireland, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Dublin , Ireland
– name: 6 Science Foundation Ireland (SFI) , Dublin , Ireland
– name: 7 Tuberculosis Diagnostics and Immunology Research Centre, UCD School of Veterinary Medicine, University College Dublin , Dublin , Ireland
– name: 1 Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin , Dublin , Ireland
– name: 3 IdentiGEN Ltd. , Dublin , Ireland
– name: 5 UCD School of Veterinary Medicine, University College Dublin , Dublin , Ireland
– name: 8 UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin , Dublin , Ireland
– name: 9 Smurfit Institute of Genetics, Trinity College , Dublin , Ireland
Author_xml – sequence: 1
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Keywords Mycobacterium bovis
BCG
tuberculosis
macrophage
cattle
gene interaction network
network
Language English
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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.
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Snippet Mycobacterium bovis is an intracellular pathogen that causes tuberculosis in cattle. Following infection, the pathogen resides and persists inside host...
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SubjectTerms BCG
Cattle
Immunology
macrophage
Mycobacterium bovis
network
Tuberculosis
Title Key Hub and Bottleneck Genes Differentiate the Macrophage Response to Virulent and Attenuated Mycobacterium bovis
URI https://www.ncbi.nlm.nih.gov/pubmed/25324841
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