MHC-Y Directed Immune Responses during Colonization of Chickens by Campylobacter

Campylobacter spp. infections are presently among the most common bacterial infections associated with human gastroenteritis worldwide. Poultry products are the major source of infection. Withisolates increasingly found to be resistant to antimicrobials, Campylobacter jejuni is now classified as an antimicrobial threat. The major goal of this project is to find new means for reducing the presence of C. jejuni in poultry food products. Campylobacter bacteria colonize the chicken intestine (especially caeca), often growing to high numbers, while having little or no affect on bird health. Multiple studies have demonstrated that genetic lineage in chickens strongly affects colonization, but the responsible genes are not identified. The focus of this project is on defining the role of MHC-Y genetics in the observed differences in colonization of chickens by Campylobacter. The MHC-YF class I-like genes are candidate loci for affecting colonization. MHC YF gene expression is frequently reported to change following Campylobacter colonization. Recently it has become clear that these chicken MHC class I-like molecules are structurally most similar to the mammalian MR1 molecules that present microbial riboflavin metabolites to innate-like mucosal-associated invariant T (MAIT) cells. Chicken YF molecules may function in a similar manner although they instead bind bacterial lipids. Chicken YF molecules, in contrast to MR1, are highly polymorphic. It could be that some isoforms are more effective than others in guiding host responses. This project is focused on testing the hypothesis that MHC-Y genetics contributes to the early immune responses that occur in newly-hatched chicks and that MHC-Y has a role in determiningcolonization by Campylobacter and other bacteria. The supporting objectives are:To investigate the contribution of MHC-Y in resistance to Campylobacter colonization correlating the level of colonization of individual animals with the MHC-Y genotypes.To characterize polymorphic features of MHC-Y haplotypes focusing on the expressed polymorphic YF genes.To gain insight into the function of YF MHC class I-like molecules selected isoforms will be tested 1) in molecular recognition assays to define specificity in their recognition and b) in binding assays to define the specificity of ligand bound.