Innate immunity
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
In vertebrates, innate immune responses have a profound effect on conditioning the type of adaptive immune response that is induced by infection. We aim to characterise the biology of the cells of the innate immune system and gain greater understanding of the mechanisms involved in specific pathogen recognition. We will also develop means to manipulate innate immune function. The Objectives of the theme are: To characterise the basic biology of cells of the innate immune systems of animals. To understand the mechanisms involved in specific pathogen recognition. To identify and test means to manipulate innate immune function.
Planned Impact
unavailable
Organisations
People |
ORCID iD |
| Ivan Morrison (Principal Investigator) |
Publications
Bell CR
(2014)
Evidence of a high incidence of subclinically affected calves in a herd of cattle with fatal cases of Bovine Neonatal Pancytopenia (BNP).
in BMC veterinary research
Bishop RP
(2015)
The African buffalo parasite Theileria. sp. (buffalo) can infect and immortalize cattle leukocytes and encodes divergent orthologues of Theileria parva antigen genes.
in International journal for parasitology. Parasites and wildlife
Connelley T
(2011)
NKp46 defines ovine cells that have characteristics corresponding to NK cells.
in Veterinary research
Connelley TK
(2011)
Escape from CD8+ T cell response by natural variants of an immunodominant epitope from Theileria parva is predominantly due to loss of TCR recognition.
in Journal of immunology (Baltimore, Md. : 1950)
Connelley TK
(2014)
Genomic analysis offers insights into the evolution of the bovine TRA/TRD locus.
in BMC genomics
Connelley TK
(2014)
NKp46+ CD3+ cells: a novel nonconventional T cell subset in cattle exhibiting both NK cell and T cell features.
in Journal of immunology (Baltimore, Md. : 1950)
Hart J
(2017)
Identification of immediate early gene products of bovine herpes virus 1 (BHV-1) as dominant antigens recognized by CD8 T cells in immune cattle.
in The Journal of general virology
Hemmink JD
(2018)
Ancient diversity and geographical sub-structuring in African buffalo Theileria parva populations revealed through metagenetic analysis of antigen-encoding loci.
in International journal for parasitology
| Description | Macrophage colony-stimulating factor (CSF-1) and IL34 bind to the same receptor (CSF1R) and control growth and differentiation of macrophages. We showed that this two ligand/one receptor system is conserved in birds and demonstrated that the two ligands must bind distinct regions of the receptor (Garceau et al. J.Leukocyte Biology 87:753-764). We have also cloned and expressed CSF-1, IL34 and the receptor from the pig and (supported by Pfizer Animal Health) have used these proteins to generate macrophages from the pig and chicken, to characterise their gene expression profiles. We have also made monoclonal antibodies against the CSF-1 receptors of pigs and chickens, which, based upon findings in mice (MacDonald et al. Blood 116:3955-63), should be useful in defining monocyte subsets and their functions in these livestock species. - Comparative aspects of constitutive and inducible gene expression profiles in macrophages from mice, pigs, humans and chickens have been explored using combinations of array profiling, RNA sequencing and genome-scale 5'RACE. Studies of the function of macrophage-expressed genes have identified a novel cytoplasmic receptor for DNA, AIM2 (Roberts et al. Science 323:1057-1060) and elucidated a myelo-suppressive function for schlafen 4 (Van Zuylen et al. PLoS One 6:e15723). - The Jmjd6 protein is upregulated in inflammatory activated and hypoxic macrophages. Protein interaction screens have led to the identification of a new function of the Jmjd6 protein in the regulation of DNA splicing (Webby et al., Science 325: 90-93). Jmjd6 was found to catalyse hydroxylation of the splicing factors U2AF65 and LUC7L2 in an oxygen-dependent manner which influences alternative splicing of a number of hypoxia response genes (Boeckel et al., PNAS. 108: 3276-81). - Comparative genomic analyses of the evolving toll-like receptor (TLR) family (Jann et al. BMC Genomics, 10:219+) across mammalian and bird species reveals clear divergence of ligand recognition surfaces across species. These analyses indicate that the selective pressures on ruminant TLR2 are distinct from other mammals, resulting in changes in structure and potentially ligand binding (Werling et al. Trends Immunol., 30:124-130). These findings have implications for vaccine design as they suggest that species-specific ligands may be required for effective adjuvancy. |
| Exploitation Route | Further research. |
| Sectors | Agriculture Food and Drink Healthcare |