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Molecular Genomics

Constitutive Differences in Gene Expression Profiles Parallel Genetic Patterns of Susceptibility to Tuberculosis in Mice

Marianna O. Orlova, Konstantin B. Majorov, Irina V. Lyadova, Eugenii B. Eruslanov, Cyr E. M'lan, Celia M. T. Greenwood, Erwin Schurr, Alexander S. Apt
Marianna O. Orlova
1Laboratory for Immunogenetics, Central Institute for Tuberculosis, Yauza Alley 2, Moscow 107564, Russia
2McGill Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, Montreal, H3G 1A4 Quebec, Canada
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Konstantin B. Majorov
1Laboratory for Immunogenetics, Central Institute for Tuberculosis, Yauza Alley 2, Moscow 107564, Russia
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Irina V. Lyadova
1Laboratory for Immunogenetics, Central Institute for Tuberculosis, Yauza Alley 2, Moscow 107564, Russia
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Eugenii B. Eruslanov
1Laboratory for Immunogenetics, Central Institute for Tuberculosis, Yauza Alley 2, Moscow 107564, Russia
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Cyr E. M'lan
3Program in Genetics and Genomic Biology, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
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Celia M. T. Greenwood
3Program in Genetics and Genomic Biology, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
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Erwin Schurr
2McGill Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, Montreal, H3G 1A4 Quebec, Canada
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Alexander S. Apt
1Laboratory for Immunogenetics, Central Institute for Tuberculosis, Yauza Alley 2, Moscow 107564, Russia
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  • For correspondence: asapt@aha.ru
DOI: 10.1128/IAI.00196-06
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    FIG. 1.

    Expression of Il-11 and Cxcl-14 by lung macrophages and fibroblasts isolated from TB-susceptible I/St mice and TB-resistant A/Sn mice. Normalized Il-11 and Cxcl-14 gene expression levels are shown as severalfold differences relative to Hprt gene expression. (A) Lung macrophages (gray bars) express higher levels of Il-11 than lung fibroblasts (hatched bars) from both I/St and A/Sn mice. (B) Lung fibroblasts (hatched bars) express higher levels of Cxcl-14 than macrophages (gray bars) from mice of both strains. In each experiment, syngeneic lung macrophages or lung fibroblasts extracted from several mice were pooled. Expression levels of Il-11 and Cxcl-14 were measured by quantitative RT-PCR. Results are expressed as means (±standard errors) of triplicate assays from one of three experiments with similar results.

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  • TABLE 1.

    Partial list of genes differentially expressed in I/St and A/Sn macrophagesa

    GeneScore (d) forb:Protein or geneeAccession no.Gene name
    Control cellscInfected cellsd
    Chemokine and cytokine genes
        Scyb14f10.45.3Cxcl14, macrophage inflammatory protein 2 gamma AW120786 96953_at
        Il-11f9.93.4Interleukin 11 U03421 92266_at
        Scyb13f7.46.1Cxcl13, B-cell homing chemokine AF030636 102025_at
        Ccr5NS2.4Chemokine (C-C motif) receptor 5 AF022990 161968_f_at
        Scya113.6NSSmall chemokine (C-C motif) ligand 11 (eotaxin-1) U77462 92742_at
        Il-6f3.5NSInterleukin 6 X54542 102218_at
        Scyb2 MIP-2a3.2NSCxcl-2, macrophage inflammatory protein 2 alpha X53798 101160_at
        Scyb1 MIP-22.8NSCxcl-1, macrophage inflammatory protein 2 L12030 95349_g_at
        Il-17−5.6NSInterleukin 17 U35108 99349_at
        Scyb10−3.0NSCxcl-10, macrophage interferon-activated protein 10 (IP-10) M33266 93858_at
        Scyb9−2.9NSCxcl-9, monokine induced by gamma interferon (Mig) M34815 101436_at
    Immune response genes
        Ifi2057.73.0Interferon-activated gene 205 M74123 94224_s_at
        Ifi202a5.32.0Interferon-activated gene 202A AV229143 94774_at
        Saa3f5.03.5Serum amyloid A 3 X03505 102712_at
        Gbp2−4.8−2.0Guanylate nucleotide binding protein 2 AJ007970 104597_at
        Chi3l3NS3.9Chitinase 3-like 3 M94584 92694_at
        Gbp1−5.1NSGuanylate nucleotide binding protein 1 M55544 95974_at
        Psmb9−4.8NSProteosome (prosome macropain) subunit beta type 9 D44456 93085_at
        Ifit2−4.4NSInterferon-induced protein with tetratricopeptide repeats 2 U43085 103639_at
        Mx2−4.2NSMyxovirus (influenza virus) resistance 2 J03368 102699_at
        Gbp3−3.4NSGuanylate nucleotide binding protein 3 AW047476 103202_at
        Mx1−3.4NSMyxovirus (influenza virus) resistance 1 M21038 98417_at
        Ifi47−3.2NSGamma interferon-inducible protein M63630 104750_at
    Cytoskeletal/extracellular matrix genes
        Mglap3.92.4Matrix gamma-carboxyglutamate (gla) protein D00613 93866_s_at
        Csrp1NS2.9Cysteine-rich protein 1 D88793 92608_at
        Adam8NS2.7A disintegrin and metalloprotease domain 8 X13335 103024_at
        Coro1aNS2.1Coronin actin binding protein 1A AW122039 96648_at
        Mmp8fNS−2.4Matrix metalloproteinase 8 U96696 94769_at
        Cldn43.2NSClaudin 4 AB000713 101410_at
    Receptor/cell surface genes
        Fpr15.22.3Formyl peptide receptor 1 L22181 99387_at
        Tm7sf1−6.7−7.0Transmembrane 7 superfamily member 1 AI060729 103017_at
        Marco−5.1−2.1Macrophage receptor with collagenous structure U18424 102974_at
        Cd22−5.0−3.0CD22 antigen L02844 102939_s_at
        Il-7r−3.6−5.5Interleukin 7 receptor M29697 99030_at
        Il1rl1NS−2.5Interleukin 1 receptor-like 1 Y07519 98501_at
        Taa17.8NSTumor-associated antigen 1 U35836 94643_at
        Tnfrsf94.6NSTumor necrosis factor receptor superfamily member 9 AA798611 103509_at
        Bdkrb3.6NSBradykinin receptor beta L26047 101748_at
        Raet1c3.3NSRetinoic acid early transcript gamma D64162 102649_s_at
        Pira13.1NSPaired-immunoglobulin-like receptor A1 U96682 95784_at
        Ly6a−4.3NSLymphocyte antigen 6 complex locus A X04653 93078_at
        Itpr5−3.2NSInositol 145-triphosphate receptor 5 AF031127 101441_i_at
        Ifngr−3.2NSGamma interferon receptor M28233 99334_at
        Csf2rb1−3.0NSColony-stimulating factor 2 receptor beta 1 M34397 94748_g_at
    • ↵ a Expression levels of genes in I/St macrophages are given relative to A/Sn macrophages, with negative numbers indicating that the gene is expressed at a higher level in A/Sn macrophages.

    • ↵ b NS, not significant.

    • ↵ c Relative interstrain difference in gene expression in uninfected macrophages.

    • ↵ d Relative interstrain difference in gene expression in infected macrophages.

    • ↵ e Protein name abbreviation is given in case it differs from the gene name.

    • ↵ f Results for these genes were confirmed by quantitative real-time assay.

  • TABLE 2.

    Real-time reverse transcription-PCR confirmation of array data

    GeneIn vitro infection with M. tuberculosisExpression level for I/St vs A/Sn macrophages
    PCRaMicroarrayb
    Il-11 −8.95.0
    +7.63.7
    Il-6 −3.62.1
    +4.52.2
    Mmp8 −−3.4cNSd
    +−5.4−2.1
    Cxcl14 −11.14.2
    +9.63.5
    Cxcl13 −28.15.1
    +30.77.2
    Saa3 −9.32.5
    +12.32.3
    • ↵ a Mean fold change in expression level for three experiments.

    • ↵ b Fold change in gene expression revealed by SAM analysis of three microarray hybridization sets.

    • ↵ c Negative numbers indicate that the gene is expressed at a higher level in A/Sn macrophages.

    • ↵ d NS, not significant.

Additional Files

  • Figures
  • Tables
  • HTML Page - index.htslp

    Files in this Data Supplement:

    • Supplemental file 1 - List of genes differently expressed in I/St and A/Sn lung macrophages
      MS Word document, 524K.
    • Supplemental file 2 - List of primers and probes used for real-time RT-PCR
      MS Word document, 45K.
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Constitutive Differences in Gene Expression Profiles Parallel Genetic Patterns of Susceptibility to Tuberculosis in Mice
Marianna O. Orlova, Konstantin B. Majorov, Irina V. Lyadova, Eugenii B. Eruslanov, Cyr E. M'lan, Celia M. T. Greenwood, Erwin Schurr, Alexander S. Apt
Infection and Immunity May 2006, 74 (6) 3668-3672; DOI: 10.1128/IAI.00196-06

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Constitutive Differences in Gene Expression Profiles Parallel Genetic Patterns of Susceptibility to Tuberculosis in Mice
Marianna O. Orlova, Konstantin B. Majorov, Irina V. Lyadova, Eugenii B. Eruslanov, Cyr E. M'lan, Celia M. T. Greenwood, Erwin Schurr, Alexander S. Apt
Infection and Immunity May 2006, 74 (6) 3668-3672; DOI: 10.1128/IAI.00196-06
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KEYWORDS

Gene Expression Profiling
Genetic Predisposition to Disease
macrophages
tuberculosis

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