Paratuberculosis (Johne's disease) is a chronic intestinal condition of ruminants caused by Mycobacterium avium subspecies paratuberculosis (Map). Map gives rise to three different forms of intestinal pathology:

1. Infected but asymptomatic - showing no sign of clinical disease.
2. Paucibacillary or tuberculoid form, affecting about 30% of clinical cases - is a granulomatous disease with a marked lymphocyte infiltrate, few mycobacteria and high T cells numbers
3. Multibacillary or lepromatous form, affecting 70% of clinical cases - is characterised by presence of a macrophage infiltrate containing many mycobacteria and few T cells.

Several studies have described some of the immunological features that are unique to each pathological form. In this study we hope to build on these findings. In paratuberculosis, as in tuberculosis and leprosy, the response of the macrophage is thought to be pivotal to the outcome of the bacterial infection. Using "functional genomic" (microarray) we aim to characterise the transcriptome signature of alveolar macrophages, derived from sheep showing the three forms of Map. This technology will test two hypotheses:

1. There are intrinsic differences in the way that macrophages respond to Map infection in the three forms of the disease (asymptomatic, paucibacillary and multibacillary).
2. Differences in the immuno-inflammatory gene expression in gut-associated lesions are directly related to the different pathological forms of the disease.

To address these two hypotheses, we have designed an immuno-inflammatory oligonucleotide microarray, which will measure the expression of more than 450 different ruminant immuno-inflammatory genes in the three forms of the disease. In developing this microarray we have produced a first generation chip; the Ruminant Immuno-inflammatory Gene Reference Array (RIGRA). This is being used for initial validation and to examine intrinsic variations in gene expression.