Differential cytokine gene expression profiles in the three pathological forms of sheep paratuberculosis

Three pathological forms of sheep paratuberculosis were defined on the basis of histopathology, cytochemistry (Zeihl-Neelsen) and IS900 PCR. Paucibacillary lesions have largely T cell and eosinophil infiltration and are ZN negative; multibacillary lesions have macrophage infiltration and large numbers of acid-fast bacteria. The pauci- and multibacillary forms are linked to the differential expression of IFNγ and IL-10 respectively. In addition the increased levels of the proinflammatory cytokines (IL-1β and TNFα), IL-8, IL-18 and TRAF-1 in both diseased forms is indicative of persistent inflammatory lesions. No changes were seen in IL-1α in any sheep ileum tissues. Asymptomatic animals are IS900+ with normal histology but have significantly decreased levels of IL-18 and increased levels TNFα.We have quantified the expression levels of thirteen cytokine and cytokine related genes in three forms of ovine paratuberculosis using real-time PCR analyses and confirm that sheep pauci- and multibacillary disease are linked to type 1 and type 2 T cell responses respectively. The expression patterns of other cytokines shows that both disease forms have an inflammatory aetiology but that the central role for IL-1α in bovine paratuberculosis is not seen in the sheep infection. Asymptomatic animals are infected and show no pathology but can be distinguished, in terms of cytokine expression pattern, from uninfected controls.Paratuberculosis (Johne's disease) is a chronic intestinal disease of ruminants caused by the bacterium Mycobacterium avium subspecies paratuberculosis. The disease is responsible for extensive economic losses worldwide related to fatality and loss of productivity [1,2]. The route of disease transmission is mainly faecal-oral; and neonates, when not infected congenitally are infected by ingestion of bacteria from infected teats or the pasture transmitted via the dissemination of diarrhoea from infected animals [3]. Consequently the majority of animals within an