Submitted to: Research Workers in Animal Diseases Conference Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 10/10/2004
Publication Date: 12/7/2004
Citation: Coussens, P.M., Pudrith, C.B., Ren, X., Skovgaard, K., Heegaard, P., Stabel, J.R. 2004. Differential Expression of genes encoding TH2 cytokines, Matrix Metalloproteinases and their inhibitors, and Regulators of Apoptosis in PBMCS of Cattle infected with M. avium subspecies paratuberculosis. Research Workers in Animal Diseases Conference Proceedings. Interpretive Summary:
Technical Abstract: Infection of ruminants with Mycobacterium avium supspecies paratuberculosis (MAP) leads to a chronic and often fatal granulomatous enteritis known as Johne's disease. Once established, infections with MAP typically exist in a subclinical state for several years. Recent cDNA microarray studies suggested that inherent gene expression profiles in peripheral blood mononuclear cells (PBMCs) from MAP infected cattle may be different from those in PBMCs from uninfected controls. In this report, we describe studies aimed at testing this hypothesis. Our novel results indicate that expression profiles of at least 42 genes are inherently different in freshly isolated PBMCs from MAP infected cattle when compared to similar cells from uninfected controls. Major classes of genes differentially expressed include those encoding cytokines and their receptors (IL-5, TGF-beta, and GM-CSF), matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) (TIMP1, TIMP2, MMP14, and MMP15), and proteins regulating apoptosis (Bad, CIDE-A, and MCL1). Gene expression differences in each of these categories were verified and expanded upon by Q-RT-PCR. Our results indicate that T cells in PBMCs from MAP infected cows exhibit a predominate Th 2-like phenotype, that cells in infected cow PBMCs exhibit higher expression of TIMP1 and TIMP2 RNA and lower expression of MMP14 RNA cells from healthy controls, and that cells within the PBMC population of MAP infected cows are likely poised for rapid apoptosis.