Virginia Tech
    • Log in
    View Item 
    •   VTechWorks Home
    • Fralin Life Sciences Institute
    • Scholarly Works, Fralin Life Sciences Institute
    • View Item
    •   VTechWorks Home
    • Fralin Life Sciences Institute
    • Scholarly Works, Fralin Life Sciences Institute
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Systems Biology Analysis of Gene Expression during In Vivo Mycobacterium avium paratuberculosis Enteric Colonization Reveals Role for Immune Tolerance

    Thumbnail
    View/Open
    journal_pone_0042127.pdf (4.674Mb)
    Downloads: 413
    Date
    2012-08-17
    Author
    Khare, Sangeeta
    Lawhon, Sara D.
    Drake, Kenneth L.
    Nunes, Jairo E. S.
    Figueiredo, Josely F.
    Rossetti, Carlos A.
    Gull, Tamara
    Everts, Robin E.
    Lewin, Harris A.
    Galindo, Cristi L.
    Garner, Harold R.
    Adams, Leslie Garry
    Metadata
    Show full item record
    Abstract
    Survival and persistence of Mycobacterium avium subsp. paratuberculosis (MAP) in the intestinal mucosa is associated with host immune tolerance. However, the initial events during MAP interaction with its host that lead to pathogen survival, granulomatous inflammation, and clinical disease progression are poorly defined. We hypothesize that immune tolerance is initiated upon initial contact of MAP with the intestinal Peyer's patch. To test our hypothesis, ligated ileal loops in neonatal calves were infected with MAP. Intestinal tissue RNAs were collected (0.5, 1, 2, 4, 8 and 12 hrs post-infection), processed, and hybridized to bovine gene expression microarrays. By comparing the gene transcription responses of calves infected with the MAP, informative complex patterns of expression were clearly visible. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis, and genes were grouped into the specific pathways and gene ontology categories to create a holistic model. This model revealed three different phases of responses: i) early (30 min and 1 hr post-infection), ii) intermediate (2, 4 and 8 hrs post-infection), and iii) late (12 hrs post-infection). We describe here the data that include expression profiles for perturbed pathways, as well as, mechanistic genes (genes predicted to have regulatory influence) that are associated with immune tolerance. In the Early Phase of MAP infection, multiple pathways were initiated in response to MAP invasion via receptor mediated endocytosis and changes in intestinal permeability. During the Intermediate Phase, perturbed pathways involved the inflammatory responses, cytokine-cytokine receptor interaction, and cell-cell signaling. During the Late Phase of infection, gene responses associated with immune tolerance were initiated at the level of T-cell signaling. Our study provides evidence that MAP infection resulted in differentially regulated genes, perturbed pathways and specifically modified mechanistic genes contributing to the colonization of Peyer's patch.
    URI
    http://hdl.handle.net/10919/48994
    Collections
    • Scholarly Works, Fralin Life Sciences Institute [542]

    If you believe that any material in VTechWorks should be removed, please see our policy and procedure for Requesting that Material be Amended or Removed. All takedown requests will be promptly acknowledged and investigated.

    Virginia Tech | University Libraries | Contact Us
     

     

    VTechWorks

    AboutPoliciesHelp

    Browse

    All of VTechWorksCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    Log inRegister

    Statistics

    View Usage Statistics

    If you believe that any material in VTechWorks should be removed, please see our policy and procedure for Requesting that Material be Amended or Removed. All takedown requests will be promptly acknowledged and investigated.

    Virginia Tech | University Libraries | Contact Us