Dissection of the molecular mechanisms leading to amyloid arthropathy in chickens

• Applicant: Dr. Clemens Falker-Gieske
• Subject Area: Animal Breeding, Animal Nutrition, Animal Husbandry
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 529325760

Amyloid arthropathy in chickens is a disease, which is caused by bacterial infection with Enterococcus faecalis (E. faecalis). The disease is characterized by protein deposits, termed amyloid, in the knee joints of affected birds. The deposits mainly consist of aggregated serum amyloid A (SAA) protein and cause lameness and eventually lead to death due to problems in feed intake. The general course of treatment is antibiosis. The overuse of antibiotics in the poultry industry is a huge burden for animals and is a major contributor to the emergence of multi-drug resistant bacteria. Multi-drug resistant E. faecalis cause approximately 200,000 annual deaths worldwide. To limit the use of antibiotics in egg production, it is important to unravel the molecular disease mechanisms of amyloid arthropathy. Brown egg-laying chickens are susceptible to amyloid arthropathy, while white egg-laying chickens are resistant to the disease. Differences in the immune response between these two types of chickens were observed, but genetic differences that make white egg-laying chickens resistant to the disease remain unknown. We have discovered a mutation in the gene that encodes the SAA protein in white egg-laying chickens. This mutation changes a single amino acid at position 90 in the protein from serine to arginine (SAA.R90S). Experiments in chicken liver cell lines revealed that SAA.R90S was expressed and secreted at higher levels than the wildtype form of the protein. Further analysis showed that the protein was not functioning properly, likely because it is not able to associate with high-density lipoproteins (HDL). SAA needs to associate with HDL to fulfill its immunogenic functions and to travel to the site of infection. In the scope of this research proposal, we plan to investigate whether SAA.R90S has lost its ability to associate with HDL, which could explain the absence of SAA deposits in the knee joints of white egg-laying chickens that have been infected with E. faecalis. The exact mechanism of SAA release from HDL is still unknown and will be studied as part of this research proposal. In addition, we will investigate whether SAA.R90S lost its ability to induce a cell fate change from CD4+ T cells to T helper 17 cells. This could explain why there are differences in the immune response between brown and white egg-laying chickens when they are infected with E. faecalis. And finally, we will perform in vivo experiments to identify the proteins that promote the formation of amyloid deposits and to gain a deeper understanding of the differences in the immune response between the two types of chickens. The knowledge gained from these experiments will form the basis for the development of treatments, prevention strategies, and breeding programs to reduce the occurrence of amyloid arthropathy in chicken flocks. In conclusion, this research has the potential to significantly improve animal welfare by reducing the occurrence of chicken amyloid arthropathy.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Jens Tetens