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Gene expression profiles during subclinical Mycobacterium avium subspecies paratuberculosis infection in sheep can
Auriol C Purdie1, Karren M Plain2, Douglas J Begg2
1Farm Animal Health, Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Sydney, Australia. auriol.purdie@sydney.edu.au.
Abstract:
Paratuberculosis in ruminants is caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP) however exposure does not predetermine progression to clinical disease. The pathogenesis incorporates a subclinical phase during which MAP is capable of evading host immune responses through adaptation of host cellular immune mechanisms. Presented are results of transcriptomic analysis of Merino sheep experimentally exposed to MAP and repeatedly sampled over the subclinical phase, identifying genes consistently changed over time in comparison to unexposed controls and associated with different disease outcomes. MAP exposed sheep were classified as diseased 45% (n = 9) or resilient 55% (n = 11). Significant gene expression changes were identified in the white blood cells of paucibacillary (n = 116), multibacillary (n = 98) and resilient cohorts (n = 53) compared to controls. Members of several gene families were differentially regulated, including S100 calcium binding, lysozyme function, MHC class I and class II, T cell receptor and transcription factors. The microarray findings were validated by qPCR. These differentially regulated genes are presented as putative biomarkers of MAP exposure, or of the specified disease or resilience outcomes. Further, in silico functional analysis of genes suggests that experimental MAP exposure in Merino sheep results in adaptations to cellular growth, proliferation and lipid metabolism.
Insights
Mycobacterium avium subspecies paratuberculosis (MAP) causes paratuberculosis in sheep, but not all exposed animals develop disease. Gene expression analysis identified biomarkers indicating MAP exposure, disease progression, or resilience in sheep.
Area of Science:
- Veterinary immunology
- Ruminant infectious diseases
- Transcriptomics
Background:
- Paratuberculosis in ruminants is caused by Mycobacterium avium subspecies paratuberculosis (MAP).
- Host immune evasion occurs during the subclinical phase of MAP infection.
- Individual responses to MAP exposure vary, with some animals developing clinical disease while others remain resilient.
Purpose of the Study:
- To identify gene expression changes in Merino sheep experimentally exposed to MAP during the subclinical phase.
- To discover potential biomarkers associated with MAP exposure, disease outcome, or resilience.
- To understand the host's cellular adaptations to MAP infection.
Main Methods:
- Transcriptomic analysis of white blood cells from Merino sheep experimentally exposed to MAP.
- Repeated sampling over the subclinical phase to track gene expression changes over time.
- Classification of sheep into diseased (paucibacillary, multibacillary) and resilient groups based on outcomes.
- Validation of microarray findings using quantitative PCR (qPCR).
Main Results:
- Significant gene expression differences were observed in diseased and resilient sheep compared to controls.
- Key differentially regulated gene families include S100 calcium binding, lysozyme, MHC class I and II, and T cell receptor.
- Gene expression patterns suggest adaptations in cellular growth, proliferation, and lipid metabolism in response to MAP exposure.
Conclusions:
- Specific gene expression profiles can serve as biomarkers for MAP exposure and predict disease or resilience outcomes in sheep.
- MAP infection induces significant alterations in host cellular immune mechanisms, impacting various biological pathways.
- Understanding these molecular changes provides insights into paratuberculosis pathogenesis and potential intervention strategies.
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