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The role of respiratory viral infection and extracellular DNA in allergic sensitisation

Lawler, Danielle Suzanne (2018) The role of respiratory viral infection and extracellular DNA in allergic sensitisation. Honours thesis, Murdoch University.

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The correlation between allergic disease and viral infections has been well established. While respiratory viral infections are strongly correlated with the development of allergic asthma, it is not known precisely how viral infection may produce, or alternatively protect, against allergic disease. Furthermore, little is known about the impact of viral infection on IgE sensitisation, due to conflicting and limited research. Recently, neutrophil extracellular traps (NETs) have been observed in viral infections and shown to induce a Th2 response. We aim to explore the link between virus infection and allergy and test if the link is mediated through NETs. We hypothesise that NETs are induced during viral respiratory infections, but that they do not adequately control the viral disease. Instead, they contribute to the development of allergic disease, and their removal will be beneficial to patients.

This hypothesis was addressed by sensitising rats to ovalbumin (OVA), during a respiratory viral infection and re-exposing the animals to OVA one week after sensitisation. To test the involvement of NETs, DNase-I was administered during viral infection to degrade NETs. OVA-specific IgE serum levels, along with cellular infiltrates into the airways, were compared between groups to assess allergic sensitisation before and after OVA re-exposure.

Although no effect on IgE sensitisation was observed with viral infection, DNase treatment reduced the risk of IgE sensitisation and increased T regulatory cell (Treg) proportions in the airways, which also displayed higher levels of FoxP3. We did not observe a difference between any of the groups in respect to allergic recall response suggesting that the achieved sensitisation was not sufficient to induce clinical disease. Our findings nevertheless suggest that DNase treatment induces a regulatory response, which may protect against allergic disease. Future studies should explore this immunoregulatory response, as a novel strategy for allergy protection.

Item Type: Thesis (Honours)
Murdoch Affiliation(s): School of Veterinary and Life Sciences
United Nations SDGs: Goal 3: Good Health and Well-Being
Supervisor(s): Leffler, Jonatan and Currie, Andrew
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