The role of natural killer cells in modulating the immune response in bovine E. coli mastitis

• Applicant: Dr. Anja Sipka
• Subject Area: Veterinary Medical Science ; Immunology
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246128117

The inflammation of the mammary gland is an economically important disease in dairy cows leading to high losses in the dairy industry. Especially infections with gram negative pathogens can cause serious clinical conditions which may, in severe cases, lead to the death of the animal. Among gram negative bacteria, E. coli is one of the best characterized mastitis pathogens and most common in well managed dairy farms. Although it is known that the different strains influence the clinical outcome, the amplitude of the inflammatory response is mainly determined by host factors of the cow. Up to date the immune response during mastitis is poorly understood. Despite intensive research available vaccines can only decrease severity of clinical symptoms but not effectively prevent disease. It is believed that events during the early phase of the immune response are most important for the outcome of the disease. Innate immune mechanisms play a critical role in this phase of the inflammation. Natural Killer (NK) cells belong to the innate immune system and are mainly known for their ability to directly kill infected or stressed cells. More recent studies in humans and mice show that they also influence the inflammatory response during bacterial infections by the secretion of immune modulatory mediators. In the bovine system NK cells have been sparsely investigated so far. A recently published study on gene expression profiles in udder tissue during E. coli mastitis suggests a potential role of NK cells during the immune response in mastitis. Up to date the presence of NK cells in bovine udder has not been confirmed and the immune modulatory properties of bovine NK cells are not fully understood. In preliminary data it could be shown that NK cells are present in the bovine udder and that NK cell associated genes are up regulated after infection with E. coli. The aim of this study is therefore to provide a better understanding on how the presence of NK cells influences the clinical outcome in mastitis and how they mediate their effects during a bacterial infection. In an in situ study detailed analysis of NK cell distribution in bovine udder tissue and supra mammary lymph nodes after experimentally induced E. coli mastitis will be performed. The results will be compared to the individual clinical outcome and local immunological parameters. In an in vitro set up it will be studied whether bovine NK cells can be primed by mature Dendritic Cells (DC) after stimulation with E. coli. Furthermore the ability of primed NK cells to influence the function of neutrophilic granulocytes as well as their potential direct antimicrobial properties will be investigated. The results of this study will provide deeper insight into the NK cell associated mechanisms in the early immune response and will help to develop a more holistic model of the inflammatory dynamics during E. coli mastitis.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Ynte Schukken, Ph.D.