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Pathways and Genes Associated with Immune Dysfunction in Sheep Paratuberculosis.

Anton Gossner1, Craig Watkins2, Francesca Chianini2

  • 1The Roslin Institute &R(D)SVS, University of Edinburgh, Easter Bush, Midlothian EH25 9RG. U.K.

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Summary

Mycobacterium avium subspecies paratuberculosis causes both multibacillary and paucibacillary paratuberculosis. Gene expression analysis reveals immune dysfunction, not distinct Th1/Th2 shifts, underlies disease progression.

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Area of Science:

  • Veterinary Immunology
  • Molecular Biology
  • Bacterial Pathogenesis

Background:

  • Paratuberculosis, caused by Mycobacterium avium subspecies paratuberculosis (MAP), presents in multibacillary (MB) and paucibacillary (PB) forms.
  • MB disease involves epithelioid macrophages and immune dysfunction, akin to human lepromatous leprosy.
  • PB disease exhibits T cell presence and higher cell-mediated immunity.

Purpose of the Study:

  • To characterize the immunological dysfunction in paratuberculosis using gene expression analysis.
  • To investigate differences in immune gene expression between MB and PB forms of the disease.

Main Methods:

  • TruSeq analysis of ileocaecal lymph node tissue from paratuberculosis-affected sheep.
  • Quantification of gene transcripts related to immune cell function, activation, and inflammation.

Main Results:

  • Significant repression of T cell receptor (TCR)/CD3, co-receptor, co-stimulator, activation, and signal-transduction genes.
  • Evidence of acute phase response and chronic inflammation, with minimal acute inflammation markers.
  • Elevated immunoglobulin and plasma cell transcripts, correlating with anti-MAP antibody levels.
  • Marked reduction in mast cell transcripts, potentially impacting dendritic cell (DC) activation.

Conclusions:

  • Immune dysfunction in paratuberculosis is characterized by a decline in T cell-related gene expression, rather than a Th1/Th2 shift.
  • No fundamental gene expression differences were found between MB and PB disease, suggesting a continuum of immune dysfunction.
  • The findings highlight a progressive immune impairment leading to multibacillary pathology.