The role of the host in the pathogenesis of ovine footrot

Abstract

THE ROLE OF THE HOST IN THE PATHOGENESIS OF OVINE FOOTROT – BY V BHARDWAJ Ovine footrot is a major disease affecting sheep welfare and production in Australia. Treatment with serogroup-specific fimbrial vaccination holds great promise for the control of footrot as it provides protection for several months. The manifestation of clinical signs in footrot is dependent on the interaction between the host, the pathogen and the environment. While researchers have studied the causal organism, Dichelobacter nodosus, in an attempt to understand its virulence mechanisms, very little is known about the role of the host in ovine footrot, either in the progression of natural infection or in the response to vaccination. As host factors are likely to contribute to the severity of disease in footrot, this study was undertaken to examine some aspects of the host in the pathogenesis of ovine footrot. The first aspect of the host studied was the systemic adaptive immune system (Chapter 3). Cytokines (IFN-γ and IL-10), T cells (CD4, CD5, CD8 and γδ) and B cells were studied in three groups of sheep following experimental infection with D. nodosus and fimbrial vaccination: Non Responders or sheep that did not respond to the vaccine, Responders or sheep that had disease resolution following vaccination and Non Diseased or sheep that did not develop clinical signs of footrot following experimental challenge. The immunological assays studied showed that most markers were activated following infection and vaccination but no differences were detected between the three groups of sheep. Micro-titre agglutination tests showed no difference between the three groups of sheep, but more importantly, all groups developed antibody titres in excess of the minimum titre thought to be required for protection. This study showed that disease could persist despite the presence of antibodies at high levels following vaccination. The ability of these animals to respond to antigens other than D. nodosus was also assessed (Appendix). Ovalbumin, Keyhole limpet haemocyanin and lipopolysaccharide from Escherichia coli were used as model antigens. In most cases, responses of the three groups of sheep were similar except for CD5 and B cells where the Non Responders showed greater stimulation indices than the other two groups. The biological significance of this remains unknown. The innate immune system was also studied in the three groups of sheep using a phagocytosis assay (Chapter 4). Assays were developed and optimised to assess sera and phagocytic cells from the three groups of sheep. While a trend was seen for an increased uptake of labelled D. nodosus in the Responders, there was no significant difference between the three groups of sheep. This suggests that the ability of antibodies and other serum factors to opsonise bacteria and the ability of phagocytic cells to uptake bacteria are unlikely to be the cause of differential disease outcome following vaccination. In addition, the phagocytes of all three groups of sheep were able to kill intracellular D. nodosus.