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Published on: November 9, 2017
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.
Abstract:
Mycobacterium avium subsp. paratuberculosis, the causative agent of Johne's disease, is able to dampen or distort immune responses at the mucosal sites and coexist with a massive infiltration of immune cells in the gastrointestinal tract. Knowledge of the mechanism by which M. avium subsp. paratuberculosis subverts the immune response at the mucosal level in cattle is important for the development of improved disease control strategies, including new vaccines and diagnostic tests. In this study, 38 cull cows from herds infected with M. avium subsp. paratuberculosis were divided into four groups, based on M. avium subsp. paratuberculosis culture from gut tissues and histopathological lesion scores. Cytokine gene expression and secretion from M. avium subsp. paratuberculosis sonicate-stimulated peripheral blood mononuclear cell (PBMC) and mesenteric lymph node (MLN) cultures of the animals were compared. Antigen stimulation of MLN cells from the severely lesioned group resulted in significant upregulation of the mRNA expression of five cytokines, gamma interferon (IFN-γ), interleukin-10 (IL-10), IL-13, IL-17A, and tumor necrosis factor alpha (TNF-α), which have a diverse range of functions, while there was no significant upregulation of these cytokines by the other groups. There were major differences between the responses of the PBMC and MLN cultures, with higher levels of secreted IFN-γ released from the MLN cultures and, conversely, higher levels of IL-10 released from the PBMC cultures. The upregulation of all five cytokines from cells at the site of infection in the severely lesioned animals suggested a dysregulated immune response, contributing to a failure to clear infection in this group of animals.
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