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Pan-genomic analysis of bovine monocyte-derived macrophage gene expression in response to in vitro infection with Mycobacterium avium subspecies paratuberculosis.

ABSTRACT: Mycobacterium avium subspecies paratuberculosis is the causative agent of Johne's disease, an intestinal disease of ruminants with major economic consequences. Infectious bacilli are phagocytosed by host macrophages upon exposure where they persist, resulting in lengthy subclinical phases of infection that can lead to immunopathology and disease dissemination. Consequently, analysis of the macrophage transcriptome in response to M. avium subsp. paratuberculosis infection can provide valuable insights into the molecular mechanisms that underlie Johne's disease. Here, we investigate pan-genomic gene expression in bovine monocyte-derived macrophages (MDM) purified from seven age-matched females, in response to in vitro infection with M. avium subsp. paratuberculosis (multiplicity of infection 2:1) at intervals of 2 hours, 6 hours and 24 hours post-infection (hpi). Differentially expressed genes were identified by comparing the transcriptomes of the infected MDM to the non-infected control MDM at each time point (adjusted P-value threshold ? 0.10). 1050 differentially expressed unique genes were identified 2 hpi, with 974 and 78 differentially expressed unique genes detected 6 and 24 hpi, respectively. Furthermore, in the infected MDM the number of upregulated genes exceeded the number of downregulated genes at each time point, with the fold-change in expression for the upregulated genes markedly higher than that for the downregulated genes. Inspection and systems biology analysis of the differentially expressed genes revealed an enrichment of genes involved in the inflammatory response, cell signalling pathways and apoptosis. The transcriptional changes associated with cellular signalling and the inflammatory response may reflect different immuno-modulatory mechanisms that underlie host-pathogen interactions during infection.

SUBMITTER: Machugh DE

PROVIDER: S-EPMC3411445 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Pan-genomic analysis of bovine monocyte-derived macrophage gene expression in response to in vitro infection with Mycobacterium avium subspecies paratuberculosis.

Machugh David E DE Taraktsoglou Maria M Killick Kate E KE Nalpas Nicolas C NC Browne John A JA DE Park Stephen S Hokamp Karsten K Gormley Eamonn E Magee David A DA

Veterinary research 20120328

Mycobacterium avium subspecies paratuberculosis is the causative agent of Johne's disease, an intestinal disease of ruminants with major economic consequences. Infectious bacilli are phagocytosed by host macrophages upon exposure where they persist, resulting in lengthy subclinical phases of infection that can lead to immunopathology and disease dissemination. Consequently, analysis of the macrophage transcriptome in response to M. avium subsp. paratuberculosis infection can provide valuable ins ...[more]

PMID: 22455317

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Project description:Background: Mycobacterium avium subspecies paratuberculosis (MPTb) is the causative agent of Johne’s disease, an intestinal disease of ruminants with major economic consequences. MPTb bacilli are phagocytosed by host macrophages upon exposure where they persist, resulting in lengthy subclinical phases of infection that can lead to immunopathology and disease dissemination. Consequently, analysis of the macrophage transcriptome in response to MPTb infection can provide valuable insights into the molecular mechanisms that underlie Johne’s disease. Here, we investigate pan-genomic gene expression in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro infection with MPTb (multiplicity of infection 2:1) at intervals of 2 hours, 6 hours and 24 hours post-infection. Results: Differentially expressed genes were identified by comparing the transcriptomes of the infected MDM to the control MDM at each time point (adjusted P-value threshold ≤ 0.10). 1,050 differentially expressed unique genes were identified 2 hours post-infection, with 974 and 84 differentially expressed unique genes detected 6 hours and 24 hours post-infection, respectively. Furthermore, in the infected MDM the number of upregulated genes exceeded the number of downregulated genes at each time point, with the fold-change in expression for the upregulated genes markedly higher than that for the downregulated genes. Conclusions: Inspection and systems analysis of the differentially expressed genes revealed changes in the expression profiles of genes involved in the inflammatory response, cell signalling pathways and apoptosis. The transcriptional changes associated with cellular signalling and the inflammatory response may reflect different immuno-modulatory mechanisms that underlie host-pathogen interactions during infection. Affymetrix GeneChip® Bovine Genome Arrays were used to examine gene expression of bovine monocyte-derived macrophages (MDM) after in vitro challenge with Mycobacterium avium subspecies paratuberculosis across a time series of 2 hr, 6 hr and 24 hr post-challenge. A 0 hr control treatment was also generated and seven different age-matched female Holstein-Friesian cattle were used for each time-point/treatment combination for a total of 49 microarrays, one of which was excluded from analysis since it did not pass quality control.

Dataset Information

Pan-genomic analysis of bovine monocyte-derived macrophage gene expression in response to in vitro infection with Mycobacterium avium subspecies paratuberculosis.

Publications

Pan-genomic analysis of bovine monocyte-derived macrophage gene expression in response to in vitro infection with Mycobacterium avium subspecies paratuberculosis.

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