Adhesion molecules and cytokine profile in ileal tissue of sheep infected with Mycobacterium avium subsp. paratuberculosis.

Sheep develop clinical diseases after 3-5 years after infection with Mycobacterium avium subsp. paratuberculosis (MAP). Clinical symptoms of paratuberculosis include persistent diarrhea and weight loss due to a chronic inflammation of the small intestine. Tissue alterations in the areas of the ileo-cecal junction are often observed. Here, we investigate the molecular processes underlying tissue damages in intestinal mucosa of 14 sheep showing either tuberculoid or lepromatous form of MAP enteritis. We found that E-cadherins, alpha-catenin and beta1-integrins were present at significant low levels in tissues of sheep affected by lepromatous form and that this pattern was associated with high expression of TGF-beta, IL-10, IL-1beta, and TNF-alpha and with a modest increase of CD4+ and CD25+ T cells. Tissues of sheep with the tuberculoid form showed high expression of IFNgamma, IL-12, and MCP-1 and a significant presence of CD4+ and CD25+ T cells. Finally, anti-transglutaminase (tTG) IgG1 antibodies were detected in sera of infected animal belonging to both groups, as already described for human inflammatory bowel diseases. Our results further stress the similarities in the clinical and histological features between ruminant paratuberculosis and human intestinal inflammatory diseases.