Characterisation of innate mucosal immunity during Cryptosporidium parvum infection

Newborn animals and humans are very vulnerable to infections via mucosal surfaces. Cryptosporidium parvum, a zoonotic pathogen that develops in the gut mucosa, causes profuse diarrhoea that can lead to death by dehydration. Due to the limited availability of drugs effective against the parasite, cryptosporidiosis is the primary cause of neonatal diarrhoea in calves in France and is highly prevalent in all ruminants including lambs throughout Europe. C. parvum develops in the epithelial cells of the gut mu cosa and protection is associated with interferon-gamma production. Work with a mouse model demonstrated that innate immunity could be sufficient to control the disease. Therefore, we put forward the hypothesis of a role of Natural Killer (NK) cells in ea rly host immune response. This is based on the knowledge that NK cells are the first and predominant IFN producers, especially in neonates in which a T-cell response is not yet established. NK cells are known to be present in the gut mucosa in animal mode ls but this has not been studied in sheep. The aim of the project is to get an overview of the distribution and numbers of NK cells in ovine gut mucosa and gut-associated lymphoid tissue (GALT) at homeostasis, by immunohistochemical techniques. This will give basic knowledge allowing assessment of the recruitment of NK cells in the same tissues during an infection with C. parvum. In parallel, we want to compare the phenotype and major functional properties (proliferation, cytotoxicity and production of cy tokines) of mucosal NK cells to the systemic NK cells (blood (already characterized in the adult) and spleen). In an infection model, using lambs, we will perform a comparison between healthy and infected animals and obtain data on the role of NK cells in the defence against C. parvum infection.