Key hub and bottleneck genes differentiate the macrophage response to virulent and attenuated Mycobacterium bovis

被引:17
作者
Killick, Kate E. [1 ,2 ]
Magee, David A. [1 ]
Park, Stephen D. E. [1 ,3 ]
Taralctsoglou, Maria [1 ,4 ]
Browne, John A. [1 ]
Conlon, Kevin M. [5 ,6 ]
Nalpas, Nicolas C. [1 ]
Gormley, Eamonn [7 ]
Gordon, Stephen V. [5 ,8 ]
MacHugh, David E. [1 ,8 ]
Hokamp, Karsten [9 ]
机构
[1] Univ Coll Dublin, UCD Sch Agr & Food Sci, Anim Genom Lab, Dublin 4, Ireland
[2] Univ Coll Dublin, UCD Conway Inst Biomol & Biomed Res, Syst Biol Ireland, Dublin 4, Ireland
[3] IdentiGEN Ltd, Dublin, Ireland
[4] Hlth & Safety Execut, Biol Agents Unit, Leeds, W Yorkshire, England
[5] Univ Coll Dublin, UCD Sch Vet Med, Dublin 4, Ireland
[6] Sci Fdn Ireland, Dublin, Ireland
[7] Univ Coll Dublin, UCD Sch Vet Med, TB Diagnost & Immunol Res Ctr, Dublin 4, Ireland
[8] Univ Coll Dublin, UCD Conway Inst Biomol & Biomed Res, Dublin 4, Ireland
[9] Univ Dublin Trinity Coll, Smurfit Inst Genet, Dublin 2, Ireland
基金
爱尔兰科学基金会;
关键词
Mycobacterium bovis; tuberculosis; BCG; cattle; macrophage; network; gene interaction network; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; SMALL-WORLD; TUBERCULOSIS; PATHOGEN; BCG; EXPRESSION; INFECTION; NETWORKS; PROTEIN;
D O I
10.3389/fimmu.2014.00422
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-Guerin. 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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页数:13
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