Understanding inflammatory processes in ovine footrot to inform rational vaccine design

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Footrot is one of the most important diseases affecting the health and welfare of sheep in the UK and throughout the world, and impacts on productivity and profitability within the sheep industry. It is in the top five most important diseases of sheep and globally affects the income of the poorest farmers. Approximately 14 million sheep get footrot in the UK each year. Footrot is caused by bacteria that invade the skin of the foot, and cause pain and swelling. In severe cases, the hoof horn capsule, the hard outer surface of the foot, separates from the underlying and sensitive living tissue, rather like a fingernail coming away from the finger. Affected sheep can be treated with an antibiotic injection, however to do this sheep have to be caught. Sheep are fearful animals and are very stressed by being caught and handled, so although it is good for their health and welfare to be treated, the very act of catching them to administer the treatment also reduces their welfare; 14 million treatments means a lot of very stressed sheep. If sheep are left untreated they lose weight, remain lame for some time and are less likely to become pregnant. If they do have lambs they produce less milk and so cannot feed their lambs as well as those ewes that are not lame, as well as impacting on their profitability. We know that treatment by antibiotic injection early in disease leads to dramatic recovery within a few days. In the long term however, we want to stop using antibiotics to treat farm animals so that we reduce the risk of antibiotic resistance and avoid antibiotics being present in livestock farmed for human consumption. In addition, we want to reduce stress in sheep and avoid the need to catch and treat lame sheep. Ideally, rather that treating disease, we would prefer to prevent disease by vaccination. There is a vaccine available to assist in control of footrot, but less than 10% of UK farmers use this vaccine: it is neither long lasting (5 months maximum) nor very effective (60% effective at best). This lack of effectiveness is thought to be due to a failure to stimulate the best possible host immune response. Our research will help us to understand how sheep respond to the bacteria that cause footrot during the very early stages of infection, and will ultimately help in the development of alternative approaches to preventing disease, including a new vaccine in the longer term.We will do this by studying the local immune defences in the sheep foot, how the bacteria causing footrot are recognised by the immune system and the immune response to these bacteria. In addition, we will investigate the relationships between individual strains of the bacterium that causes disease and the potential for certain strains to be associated with disease. We think that footrot might occur when the sheep immune system responds too much to the bacteria, rather like human intolerance to milk, when our gut reacts to milk proteins when it should not. Alternatively, this could be due to lack of regulation of the inflammatory response leading to excessive collateral damage to the surrounding tissues. If we are right, then this will explain why antibiotics are so good at aiding recovery from footrot - because they kill the bacteria and so reduce the sheep immune response. We will be able to see this by studying tissue samples taken from the feet of sheep affected and unaffected with footrot. We will also use tissue samples taken from healthy sheep that we will culture in the laboratory and expose to bacteria that cause footrot. By the end of this project we will be able to explain better how the clinical signs of footrot are caused and how the immune system contributes to this. This will help to inform on new approaches to disease management and ultimately disease prevention.