Expression profiling reveals differences in immuno-inflammatory gene expression between the two disease forms of...

Area of Science:

• Veterinary Immunology
• Molecular Pathology
• Ruminant Health

Background:

• Paratuberculosis is a chronic enteropathy in ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP).
• In sheep, MAP infection manifests as paucibacillary (tuberculoid) or multibacillary (lepromatous) disease, linked to immune response polarization.
• Most MAP-infected sheep remain asymptomatic, highlighting varied disease progression.

Purpose of the Study:

• To investigate the molecular differences between paucibacillary, multibacillary, and asymptomatic paratuberculosis in sheep.
• To identify key genes and pathways involved in the distinct pathologies of MAP infection.

Main Methods:

• Gene expression profiling using microarray analysis.
• Validation of candidate genes via real-time quantitative reverse transcription PCR (RT-qPCR).
• Single Nucleotide Polymorphism (SNP) analysis of selected genes (CXCR4, IGFBP6).

Main Results:

• Microarray analysis identified 36 differentially expressed genes (fold-change >1.5, P<0.05).
• Distinct molecular profiles were observed between disease forms, particularly in chemokine and chemokine receptor gene expression.
• Specific SNPs were identified, with one IGFBP6 SNP absent in asymptomatic sheep.

Conclusions:

• The two disease forms of paratuberculosis in sheep are associated with unique molecular signatures.
• Differential expression of chemokine-related genes may contribute to the distinct cellular infiltrates observed in each pathology.
• Further research into these molecular profiles can elucidate disease mechanisms and inform diagnostic strategies.