Johne's disease in cattle is associated with enhanced expression of genes encoding IL-5, GATA-3, tissue inhibitors of matrix metalloproteinases 1 and 2, and factors promoting apoptosis in peripheral blood mononuclear cells

• Published in: Veterinary immunology and immunopathology 2005-05, Vol.105 (3), p.221-234
• Main Authors: Coussens, Paul M., Pudrith, Chas B., Skovgaard, Kerstin, Ren, Xiaoning, Suchyta, Steven P., Stabel, Judith R., Heegaard, Peter M.H.
• Format: Article
• Language: English
• Subjects: Animals; apoptosis; Apoptosis - physiology; Cattle; cattle diseases; Cattle Diseases - blood; Cattle Diseases - immunology; disease detection; DNA-Binding Proteins - biosynthesis; enzyme inhibitors; Female; Functional genomics; GATA3 Transcription Factor; Gene expression; Gene Expression - immunology; Gene Expression - physiology; host-pathogen relationships; immune response; interleukin-5; Interleukin-5 - biosynthesis; Johne's disease; Leukocytes, Mononuclear - metabolism; metalloproteinases; Microarray; microarray technology; monocytes; Mycobacterium avium; Mycobacterium avium subsp. paratuberculosis; Oligonucleotide Array Sequence Analysis - veterinary; Paratuberculosis; Paratuberculosis - blood; Paratuberculosis - immunology; phenotype; reverse transcriptase polymerase chain reaction; Signal Transduction; Tissue Inhibitor of Metalloproteinase-1 - biosynthesis; Tissue Inhibitor of Metalloproteinase-2 - biosynthesis; Trans-Activators - biosynthesis
• ISSN: 0165-2427; 1873-2534
• DOI: 10.1016/j.vetimm.2005.02.009

Infection of ruminants with Mycobacterium avium subspecies paratuberculosis ( M. paratuberculosis) leads to a chronic and often fatal granulomatous enteritis known as Johne's disease. Most infections with M. paratuberculosis occur during the first 6 months of life, and there is some evidence for transmission in utero. Once established, infections typically exist in a subclinical state for several years. Recent gene-expression profiling studies suggested the hypothesis that inherent gene-expression profiles in peripheral blood mononuclear cells (PBMCs) from M. paratuberculosis-infected cattle may be different than expression profiles in PBMCs from uninfected controls. If true, this would suggest that it is possible to identify an M. paratuberculosis infection “signature” through transcriptional profiling of peripheral immune cells. In addition, identification of groups or classes of genes showing inherently different expression in PBMCs from M. paratuberculosis-infected cattle relative to PBMCs from uninfected controls might highlight important interactions between this pathogen and the host immune system. In this report, we describe studies aimed at testing this hypothesis. Our novel results indicate that, indeed expression profiles of at least 42 genes are inherently different in freshly isolated PBMCs from M. paratuberculosis-infected cattle when compared to similar cells from uninfected controls. Gene-expression differences observed following microarray analysis were verified and expanded upon by quantitative real-time PCR (Q-RT-PCR). Our results indicate that T cells within PBMCs from M. paratuberculosis-infected cows have adopted a predominant Th 2-like phenotype (enhanced expression of IL-5, GATA 3, and possibly IL-4 mRNA), that cells within infected cow PBMCs may exhibit tissue remodeling deficiencies through higher expression of tissue inhibitor of matrix metalloproteinase (TIMP) 1 and TIMP2 RNA and lower expression of matrix metalloproteinase (MMP) 14 RNA than similar cells from healthy controls, and that cells within the PBMC population of M. paratuberculosis-infected cows are likely poised for rapid apoptosis (upregulation of CIDE-A, Bad, TNFRI, and Fas).