The effect of respiratory co-infections on immune function in young calves

Supervisors: Jayne Hope, Alexander Corbishley

Project description:

Respiratory disease is one of the major drivers of economic loss, antibiotic use and poor welfare of young calves, including those on calf rearing units. Cross-bred calves, born on dairy farms, are typically moved to rearing units at 2-4 weeks of age, where they are fed milk replacer prior to weaning at around 10 weeks old. Respiratory disease rates shortly after arrival onto these units are high, due to a number of risk factors, including the mixing of calves with multiple infectious agents. It is well established that a number of respiratory pathogens can act synergistically to cause disease, whilst the immunological basis of this is attracting increasing attention 1–3. This project will focus on understanding the impact of respiratory pathogen carriage on systemic immune responses in these young calves. This will inform on the capability of these calves to respond following exposure to other infectious agents or vaccination, whilst also driving management interventions to reduce disease incidence and antibiotic use.

Whilst applications from veterinary surgeons are welcomed, the project would be suitable for applicants with a background in animal science, immunology, pathology or microbiology.

The project will make use of samples collected from calves on commercial calf rearing facilities. Deep naso-pharyngeal swabs and blood samples will be collected from calves shortly after arrival on the rearing farms. Training will be provided in animal trial study design, whilst for non-veterinary surgeons, training in animal handling and sampling will be provided.

Swabs will be screened by PCR and culture for the predominant respiratory pathogens in the UK: Infectious Bovine Rhinotracheitis, Parainfluenza Virus Type 3, Bovine Respiratory Syncytial Virus, Mycoplasma bovis, Mannheimia haemolytica, Pasteurella multocida and Histophilus somni. This will be conducted by a commercial diagnostic laboratory, and placements within this laboratory can be arranged. Alongside this, the student will work with the industrial partner in this project (see below) to contribute to development and validation of novel diagnostic tests.

Blood samples from the calves will be analysed using a variety of immunological assays to understand how carriage of multiple respiratory pathogens impacts on systemic immune responses.

Laboratory training will include: cell culture, peripheral blood mononuclear cell (PBMC) isolation, PBMC re-stimulation, cytokine analysis (ELISA and ELISpot), qPCR, flow cytometry, phagocytosis assays and killing assays. The use of transcriptomic analysis of samples will also be explored.

The lifetime performance of the sampled calves will also be available towards the end of the project and this information will provide opportunities to develop skills in mixed modelling statistical analysis to understand the impact of co-infections not only on immune function in early life, but also on production efficiency and clinical disease rates.

The industrial partner in this project is developing a diagnostic platform, that utilises novel synthetic biology approaches to nucleic acid detection. The student will spend time with the partner, learning how the field samples collected as part of this project can be used for test development and validation and the challenges and opportunities of working within a commercial laboratory environment.

References:

1.        Prysliak T, van der Merwe J, Lawman Z, et al. Respiratory disease caused by Mycoplasma bovis is enhanced by exposure to bovine herpes virus 1 (BHV-1) but not to bovine viral diarrhea virus (BVDV) type 2. Can Vet J = La Rev Vet Can. 2011;52(11):1195–202. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22547839. Accessed September 6, 2017.

2.        Agnes JT, Zekarias B, Shao M, Anderson ML, Gershwin LJ, Corbeil LB. Bovine Respiratory Syncytial Virus and Histophilus somni Interaction at the Alveolar Barrier. Infect Immun. 2013;81(7):2592–2597. doi:10.1128/IAI.00108-13.

3.        McGill JL, Rusk RA, Guerra-Maupome M, Briggs RE, Sacco RE. Bovine Gamma Delta T Cells Contribute to Exacerbated IL-17 Production in Response to Co-Infection with Bovine RSV and Mannheimia haemolytica. Varga SM, ed. PLoS One. 2016;11(3):e0151083. doi:10.1371/journal.pone.0151083.

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