Immune responses to infection and during inflammation

Rationale: This novel project will study mammalian host immune responses in the skin following infection with viruses spread by mosquitoes. These viruses are an increasing and major threat to human health on a global scale. This proposal aims to ultimately reduce the burden of these diseases by increasing our understanding of the skin’s immune defence to infection at the mosquito bite. When mosquitoes bite people they inject virus into the skin. This activates the body’s immune response, which if sufficiently robust can hinder the virus from replicating and causing disease. We have recently found that the strength and type of immune responses activated at the mosquito bite can influence how bad the infection becomes in the rest of the body. By improving our understanding of these immune responses, we aim to identify new ways of treating people who are sick. Comparisons to other inflammatory diseases of the skin, which involve similar biological processes, will also be made. 
 
Plan of work and impact of our studies: we will infect mice with viruses in the skin and define the immune responses that result. Factors that influence the susceptibility of the mammalian host to infection will be described in unprecedented detail. Uniquely, our work will determine what role factors derived from the biting mosquito has on altering the body’s response to infection. Once we identify the factors involved, we aim to use this knowledge to design and test new medicines that could protect the body against infection.
 
Animal welfare: We will always use techniques that have lowest possible impact on animal welfare. The vast majority of experiments will only result in mild and very transient suffering, such as injection with a needle. We use custom made needles that are exceptionally thin, that we believe causes less pain than conventional needles. Where appropriate, we also use temporary anaesthesia that puts the mice to sleep for a few minutes. This allows us to minimise any pain or discomfort that may be generated from the injection. To help us determine if medicines can stop mice from getting sick, we will for a small number of mice (less than 2%) allow the infection to spread to other organs, such as the brain. This can lead to brain inflammation, which results in easily detectable sickness behaviours, enabling us to rapidly remove the mice from the study and prevent unnecessary suffering.

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