Faraday earmarked proposal: Toll-like receptors and dendritic cell genetic heterogeneity
Lead Research Organisation:
University of Edinburgh
Department Name: The Roslin Institute
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
Improvement in the efficacy of vaccines and the identification of genetic traits affecting disease resistance will have a large impact on disease control in livestock. Many current vaccines are live vaccines with limited long term protection. Variable responsiveness to vaccines has been observed across populations and includes non-responsiveness as well as pathogenic responses. Disease resistance traits are also highly variable both between and within breeds. Variability in both vaccine responsiveness and disease resistance traits can have moderate to high heritability and the genes underlying these traits are likely to overlap, and involve both Major Histocompatibility Complex (MHC) and non-MHC genes. Major goals for the UK pharmaceutical and breeding industries would be to create uniformly efficacious non-live subunit vaccines for livestock and identify suitable markers for breeding for disease resistance and vaccine responsiveness. Our contention is that there will be genes underlying these traits that are expressed in the innate immune system. Specifically, this proposal will concentrate on the expression, function and polymorphism of pathogen- recognition receptors (PRR), specifically the toll-like receptors (TLR) found on authentic dendritic cells (DC) derived from cattle and sheep afferent lymph. These cells are a major component of the innate immune system and form an instructive link between the innate and acquired (adaptive, antigen-specific lymphocyte-mediated) immune systems.
Organisations
Publications
Leach, R
(2010)
Locating SNPs in the bovine genome associated with variation in the immune response
in 9th World Congress on Genetics Applied to Livestock Production
Leach, R
(2010)
Fine mapping the genetic component of the immune response to a 40-mer peptide derived from a foot-and-mouth-disease virus
in AVTRW 2010 Conference
Rowan L
(2009)
TLR expression in bovine monocytes derived from cattle breeds with differing susceptibility to tropical theileriosis
in Veterinary Immunology and Immunopathology
Smith SA
(2012)
Adaptive evolution of Toll-like receptor 5 in domesticated mammals.
in BMC evolutionary biology
Werling D
(2009)
Variation matters: TLR structure and species-specific pathogen recognition.
in Trends in immunology
Yamakawa Y
(2008)
Identification and functional characterization of a bovine orthologue to DC-SIGN.
in Journal of leukocyte biology