Host-pathogen interactions
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
The overall aim of this theme is to understand key aspects of pathogen-host cell interactions that influence the ability of the pathogens to cause disease and to induce protective immune responses. Understanding the complex interplay between host and pathogens is crucial to developing new methods for controlling infectious disease. Understanding the complex interplay between susceptible vertebrate hosts and their pathogens is crucial to developing new methods for the control of infectious disease. We aim to elucidate host and pathogen gene expression in response to infection and inflammation, and explore the interaction between pathogens and their host cells and the mechanisms by which pathogens modulate host immune function. These studies will be performed for a wide range of important animal diseases, and will include examination of vector pathogen interactions and the role of the immune system in TSE dissemination. The objectives are: To understand the interaction of intracellular pathogens with host cells and identify key events in pathogenicity. To elucidate host gene expression in response to infection and inflammation. To explore the mechanisms by which pathogens modulate host immune function. To determine the pathogen and host factors driving tissue tropism, host specificity and the induction of pathology. To determine how viruses initiate neurological disease. To determine the role of the immune system in TSE dissemination.
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
Craig NM
(2014)
Local cytokine transcription in naïve and previously infected sheep and lambs following challenge with Teladorsagia circumcincta.
in BMC veterinary research
Hayashida K
(2013)
MDM2 regulates a novel form of incomplete neoplastic transformation of Theileria parva infected lymphocytes.
in Experimental and molecular pathology
Hemmink JD
(2016)
Limited genetic and antigenic diversity within parasite isolates used in a live vaccine against Theileria parva.
in International journal for parasitology
Liu YH
(2013)
Macrophage migration is controlled by Tribbles 1 through the interaction between C/EBPß and TNF-a.
in Veterinary immunology and immunopathology
MacHugh N
(2011)
Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata
in Infection and Immunity
MacHugh ND
(2009)
CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunity.
in European journal of immunology
| Description | Comparative genomic analyses of Staphylococcus aureus isolates from human and animal species have revealed that there was a recent human to poultry host jump coinciding with a move to more intensive farming methods (Guinane et al. Genome Biol Evol 2, 454-466). This has led to the emergence of a pathogenic bacterial strain that is now endemic in poultry populations worldwide. The bacteria adapted to birds by the acquisition of mobile genetic elements from an avian S. aureus accessory gene pool. - Comparison of S. aureus isolates has also provided evidence for a human evolutionary origin for ruminant strains of S. aureus (Lowder et al. PNAS 106, 19545-50). Genome sequencing has led to the identification and functional characterization of a family of pathogenicity islands which contributes to the ruminant host-specificity of S. aureus. - Up-regulation of expression of the transcription factor c-maf, normally associated with differentiation of monocyte to macrophages, was found to be suppressed by Theileria annulata infection (Jensen et al. Int. J. Parasitol. 39, 1099-1108). Infected cells also exhibited suppression of the transcription factors, Pu.1 and RUNX1, and colony stimulating factor 1 receptor (CSF1R), which are also involved in the regulation of macrophage differentiation. These results provide the first direct evidence that T. annulata modulates the host macrophage differentiation, as well as promoting cell proliferation. - As part of an ongoing programme on development of vaccines against Theileria parasites, high throughput antigen screening systems have been developed and used successfully to identify parasite antigens recognized on infected cells by CD8 and CD4 T cells. Staining of responding CD8 T cells with class I tetramers incorporating defined epitopes demonstrated a striking immunodominance in the responses, with >60% of responding cells focused on a single dominant epitope (MacHugh et al. Eur. J. Imm. 39, 1-11). Variability in the sequence of target epitopes was shown to be under immune selection and resulted in escape from immune recognition. |
| Exploitation Route | Further research required to utilise the information for vaccine development. |
| Sectors | Agriculture Food and Drink Healthcare |