Divergent Antigen-Specific Cellular Immune Responses during Asymptomatic Subclinical and Clinical States of Disease in Cows Naturally Infected with Mycobacterium avium subsp. paratuberculosis .

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  • Author(s): Stabel JR;Stabel JR; Bannantine JP; Bannantine JP
  • Source:
    Infection and immunity [Infect Immun] 2019 Dec 17; Vol. 88 (1). Date of Electronic Publication: 2019 Dec 17 (Print Publication: 2019).
  • Publication Type:
    Journal Article; Research Support, U.S. Gov't, Non-P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0246127 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1098-5522 (Electronic) Linking ISSN: 00199567 NLM ISO Abbreviation: Infect Immun Subsets: MEDLINE
    • Publication Information:
      Publication: Washington, DC : American Society For Microbiology
      Original Publication: [Bethesda, Md.] American Society for Microbiology.
    • Subject Terms:
    • Abstract:
      Infection of the host with Mycobacterium avium subsp. paratuberculosis results in chronic and progressive enteritis that traverses both subclinical and clinical stages. The mechanism(s) for the shift from an asymptomatic subclinical disease state to advanced clinical disease is not fully understood. In the present study, naturally infected dairy cattle were divided into subclinical and clinical infection groups, along with noninfected control cows of similar parity, to study host immune responses in different stages of infection. Both infection groups had higher levels of secretion of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-2 (IL-2) than control cows, whereas only clinical cows had increased secretion of IL-10, IL-12, and IL-18 upon stimulation of peripheral blood mononuclear cells (PBMCs) with antigen. Conversely, secretion of IL-17Α was decreased for clinical cows compared to subclinical and control cows. Proinflammatory cytokine genes were upregulated only for subclinical cows, whereas increased IL-10 and IL-17 gene expression levels were observed for both infection groups. Increased CD4 + , CD8 + , and γδ T cell receptor-positive (TCR + ) T cells were observed for subclinical cows compared to clinical cows. Although clinical cows expressed antigen-specific immune responses, the profile for subclinical cows was one of a dominant proinflammatory response to infection. We reason that a complex coordination of immune responses occurs during M. avium subsp. paratuberculosis infection, with these responses shifting as the host transitions through the different stages of infection and disease (subclinical to clinical). A further understanding of the series of events characterized by Th1/Th2/Th17 responses will provide mechanisms for disease progression and may direct insightful intervention strategies.
      (This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.)
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    • Contributed Indexing:
      Keywords: Mycobacterium avium subsp. paratuberculosis; cattle; immunity
    • Accession Number:
      0 (Antigens, Bacterial)
      0 (Cytokines)
      0 (Immunologic Factors)
    • Publication Date:
      Date Created: 20191016 Date Completed: 20200122 Latest Revision: 20200617
    • Publication Date:
      20221213
    • Accession Number:
      PMC6921652
    • Accession Number:
      10.1128/IAI.00650-19
    • Accession Number:
      31611273