Global Gene Expression and Systems Biology Analysis of Bovine Monocyte-Derived Macrophages in Response to In Vitro Challenge with Mycobacterium bovis

Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection...

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Vydané v:PloS one Ročník 7; číslo 2; s. e32034
Hlavní autori: Magee, David A., Taraktsoglou, Maria, Killick, Kate E., Nalpas, Nicolas C., Browne, John A., Park, Stephen D. E., Conlon, Kevin M., Lynn, David J., Hokamp, Karsten, Gordon, Stephen V., Gormley, Eamonn, MacHugh, David E.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Public Library of Science 22.02.2012
Public Library of Science (PLoS)
Predmet:
Animal genetics
Animal populations
Animals
Apoptosis
Biology
Biomedical research
Cattle
Cellular signal transduction
Chemokines
Cytokines
Female
Females
Food science
Gene expression
Gene Expression Profiling
Gene Expression Regulation
Genes
Genetic research
Genome
Genomes
Genomics
Granuloma - metabolism
Health aspects
HIV
Human immunodeficiency virus
Immunology
In Vitro Techniques
Infection
Infections
Inflammation
Inflammatory response
Intracellular
Intracellular signalling
Kinases
Laboratories
Macrophages
Macrophages - cytology
Macrophages - microbiology
Medical research
Monocytes
Monocytes - cytology
Monocytes - microbiology
Multiplicity of infection
Mycobacterium
Mycobacterium avium
Mycobacterium bovis
Mycobacterium bovis - metabolism
Mycobacterium tuberculosis
MyD88 protein
Neutrophils
Oligonucleotide Array Sequence Analysis
Receptors
Ribonucleic acid
RNA
RNA - metabolism
Rodents
Signal Transduction
Systems analysis
Systems Biology
Toll-like receptors
Transcriptome
Tuberculosis
Tuberculosis, Bovine - microbiology
Veterinary colleges
Veterinary medicine
Ireland
ISSN:1932-6203, 1932-6203
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Abstract Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2:1). Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array. Comparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold ≤ 0.05). Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1) the inflammatory response; (2) cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3) apoptosis. The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in mediating the host response to M. bovis.
AbstractList Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2:1). Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array. Comparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold [less than or equal to]0.05). Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1) the inflammatory response; (2) cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3) apoptosis. The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in mediating the host response to M. bovis.
Background Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2:1). Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array. Results Comparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold [less than or equal to]0.05). Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1) the inflammatory response; (2) cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3) apoptosis. Conclusions The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in mediating the host response to M. bovis.
Background Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2∶1). Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array. Results Comparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold ≤0.05). Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1) the inflammatory response; (2) cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3) apoptosis. Conclusions The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in mediating the host response to M. bovis.
BACKGROUND: Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2:1). Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array. RESULTS: Comparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold ≤ 0.05). Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1) the inflammatory response; (2) cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3) apoptosis. CONCLUSIONS: The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in mediating the host response to M. bovis.
Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2:1). Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array. Comparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold ≤ 0.05). Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1) the inflammatory response; (2) cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3) apoptosis. The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in mediating the host response to M. bovis.
Background Mycobacterium bovis , the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2∶1). Total cellular RNA was extracted from non-challenged control and M. bovis -challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array. Results Comparison of M. bovis -challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P -value threshold ≤0.05). Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis -challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1) the inflammatory response; (2) cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3) apoptosis. Conclusions The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in mediating the host response to M. bovis .
Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2:1). Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array.BACKGROUNDMycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2:1). Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array.Comparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold ≤ 0.05). Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1) the inflammatory response; (2) cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3) apoptosis.RESULTSComparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold ≤ 0.05). Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1) the inflammatory response; (2) cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3) apoptosis.The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in mediating the host response to M. bovis.CONCLUSIONSThe increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in mediating the host response to M. bovis.
Audience Academic
Author MacHugh, David E.
Park, Stephen D. E.
Hokamp, Karsten
Conlon, Kevin M.
Gordon, Stephen V.
Magee, David A.
Taraktsoglou, Maria
Lynn, David J.
Nalpas, Nicolas C.
Browne, John A.
Gormley, Eamonn
Killick, Kate E.
AuthorAffiliation 6 Tuberculosis Diagnostics and Immunology Research Centre, UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland
4 Smurfit Institute of Genetics, Trinity College Dublin, Trinity College, Dublin, Ireland
1 Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, Ireland
Institut Pasteur, France
3 Animal Bioscience Centre, Teagasc, Grange, Dunsany, County Meath, Ireland
2 UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland
5 UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
AuthorAffiliation_xml – name: 3 Animal Bioscience Centre, Teagasc, Grange, Dunsany, County Meath, Ireland
– name: 1 Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, Ireland
– name: 5 UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
– name: Institut Pasteur, France
– name: 2 UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland
– name: 4 Smurfit Institute of Genetics, Trinity College Dublin, Trinity College, Dublin, Ireland
– name: 6 Tuberculosis Diagnostics and Immunology Research Centre, UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland
Author_xml – sequence: 1
  givenname: David A.
  surname: Magee
  fullname: Magee, David A.
– sequence: 2
  givenname: Maria
  surname: Taraktsoglou
  fullname: Taraktsoglou, Maria
– sequence: 3
  givenname: Kate E.
  surname: Killick
  fullname: Killick, Kate E.
– sequence: 4
  givenname: Nicolas C.
  surname: Nalpas
  fullname: Nalpas, Nicolas C.
– sequence: 5
  givenname: John A.
  surname: Browne
  fullname: Browne, John A.
– sequence: 6
  givenname: Stephen D. E.
  surname: Park
  fullname: Park, Stephen D. E.
– sequence: 7
  givenname: Kevin M.
  surname: Conlon
  fullname: Conlon, Kevin M.
– sequence: 8
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  surname: Lynn
  fullname: Lynn, David J.
– sequence: 9
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– sequence: 10
  givenname: Stephen V.
  surname: Gordon
  fullname: Gordon, Stephen V.
– sequence: 11
  givenname: Eamonn
  surname: Gormley
  fullname: Gormley, Eamonn
– sequence: 12
  givenname: David E.
  surname: MacHugh
  fullname: MacHugh, David E.
BackLink https://www.ncbi.nlm.nih.gov/pubmed/22384131$$D View this record in MEDLINE/PubMed
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Magee et al. 2012
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Conceived and designed the experiments: DAM MT JAB EG DEM. Performed the experiments: DAM MT NN JAB KMC. Analyzed the data: DAM MT KEK NN JAB SDEP DJL KH. Wrote the paper: DAM MT KEK NN DJL KH SVG EG DEM.
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Snippet Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first...
Background Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among...
BACKGROUND: Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among...
Background Mycobacterium bovis , the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among...
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SubjectTerms Animal genetics
Animal populations
Animals
Apoptosis
Biology
Biomedical research
Cattle
Cellular signal transduction
Chemokines
Cytokines
Female
Females
Food science
Gene expression
Gene Expression Profiling
Gene Expression Regulation
Genes
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Genome
Genomes
Genomics
Granuloma - metabolism
Health aspects
HIV
Human immunodeficiency virus
Immunology
In Vitro Techniques
Infection
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Inflammation
Inflammatory response
Intracellular
Intracellular signalling
Kinases
Laboratories
Macrophages
Macrophages - cytology
Macrophages - microbiology
Medical research
Monocytes
Monocytes - cytology
Monocytes - microbiology
Multiplicity of infection
Mycobacterium
Mycobacterium avium
Mycobacterium bovis
Mycobacterium bovis - metabolism
Mycobacterium tuberculosis
MyD88 protein
Neutrophils
Oligonucleotide Array Sequence Analysis
Receptors
Ribonucleic acid
RNA
RNA - metabolism
Rodents
Signal Transduction
Systems analysis
Systems Biology
Toll-like receptors
Transcriptome
Tuberculosis
Tuberculosis, Bovine - microbiology
Veterinary colleges
Veterinary medicine
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Title Global Gene Expression and Systems Biology Analysis of Bovine Monocyte-Derived Macrophages in Response to In Vitro Challenge with Mycobacterium bovis
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