Psoriasis and eczema modulate susceptibility to arbovirus infection

The climate crisis is making mosquito-borne virus infections an increasing threat to human health. These viruses, such as those that cause Zika and dengue, are infecting more people and spreading to new countries as the climate warms and globalisation helps mosquitoes spread.

These viruses are transmitted to people when biting mosquitoes spit virus into the skin. We have shown that inflammation caused by the mosquito bites helps these viruses replicate and spread around the body. We now have important new data that suggests patients with skin inflammatory disorders (psoriasis and eczema) may have different susceptibilities to these infections, and that this may relate to how immune defences are activated in the skin.

Psoriasis and eczema are debilitating skin conditions that affect approximately 3% of the global population. Skin from these patients exhibit abnormal expression of cytokines and leukocyte positioning. Patients typically require lifelong treatment with potent immune-modulating drugs (e.g. cytokine-neutralising antibodies).

Eczematous skin appears to be more susceptible to arbovirus infection, whilst psoriatic skin is less susceptible to infection. It is not clear why this is the case. Infection of the skin by these viruses represents an essential stage of virus life cycle; robust replication at this site is a pre-requisite for development of clinical disease. Aberrant positioning of the leukocytes in the skin of psoriasis/eczema patients and their ability to differentially secrete cytokines may account for differences in disease predisposition.

Objectives:
To determine in eczematous/psoriatic skin how;
1. infection with arbovirus differs (e.g. magnitude, kinetics, and cellular tropism of virus)
2. leukocyte composition and positioning within the skin and their ability to activate anti-viral immune responses differs

In doing so, this new interdisciplinary project will uniquely combine aspects of dermatology, virology and immunology. It has potential to inform individualised patient care strategies for those at risk of infection; or if infected, help stratify clinical outcome.

We also expect that the emerging knowledge from this work, on the role of skin immune responses following arbovirus infection (eczema, psoriasis and healthy skin as exemplars), will open a unique opportunity to develop protective strategies that inhibit arbovirus infection in general. i.e. these studies will help us understand what types of inflammatory responses are key for fighting virus infection.

Experimental approach:
1. We will compare ex vivo infection of human skin explants from healthy, psoriasis, eczema and treated patients. We will use Zika virus, an important and representative arbovirus, for which fluorescence expressing strains exist.
2. Inflammatory responses of skin cells will be characterised by transcriptome profiling of FACS isolated cells and validated by qPCR/immunohistochemistry.
3. In vivo experiments that target the most promising immune pathways will be performed using our established model