Diverse cytokine profile from mesenteric lymph node cells of cull cows severely affected with Johne's disease

Dairu Shu1, Supatsak Subharat, D Neil Wedlock

  • 1AgResearch, Hopkirk Research Institute, Grasslands Research Centre, Private Bag 11008, Palmerston North 4442, New Zealand. dairu.shu@agresearch.co.nz

Insights

Mycobacterium avium subsp. paratuberculosis infection in cattle causes immune dysregulation. Severely affected animals showed increased cytokine production, indicating a failure to clear the Johne's disease pathogen.

Area of Science:

  • Veterinary immunology
  • Bovine infectious diseases
  • Mycobacterial pathogenesis

Background:

  • Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease in cattle, characterized by immune suppression at mucosal sites.
  • Understanding MAP's immune evasion mechanisms is crucial for developing effective control strategies, vaccines, and diagnostics.
  • Cattle infected with MAP exhibit significant immune cell infiltration in the gastrointestinal tract.

Purpose of the Study:

  • To investigate the immune response in cattle infected with MAP.
  • To compare cytokine gene expression and secretion in peripheral blood mononuclear cells (PBMCs) and mesenteric lymph node (MLN) cells from infected cattle.
  • To identify immune markers associated with disease severity and potential failure to clear MAP infection.

Main Methods:

  • Thirty-eight cull cows from MAP-infected herds were grouped based on infection status and lesion scores.
  • Peripheral blood mononuclear cells (PBMCs) and mesenteric lymph node (MLN) cells were cultured and stimulated with MAP sonicate.
  • Cytokine gene expression (mRNA) and secretion were analyzed, comparing responses between different disease severity groups.

Main Results:

  • Antigen stimulation of MLN cells from severely lesioned cows significantly upregulated five cytokines: gamma interferon (IFN-γ), interleukin-10 (IL-10), IL-13, IL-17A, and tumor necrosis factor alpha (TNF-α).
  • PBMC and MLN cultures showed distinct cytokine profiles: MLN cultures released more IFN-γ, while PBMC cultures released more IL-10.
  • No significant cytokine upregulation was observed in less severely affected or culture-negative groups.

Conclusions:

  • The significant upregulation of multiple cytokines in MLN cells from severely lesioned cattle suggests a dysregulated immune response.
  • This immune dysregulation likely contributes to the inability to clear MAP infection in severely affected animals.
  • The distinct cytokine profiles between PBMC and MLN highlight the importance of analyzing immune responses at the site of infection.

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