Inflammasomes and interferons: new insights into the innate immune response to RSV and SARS-CoV-2 infection in airway epithelial cells

We found that although the canonical inflammasome NLRP1 is constitutively expressed and infection upregulates inflammasome-related genes, direct infection-induced activation is minimal. However, crosstalk between epithelial and immune cells significantly potentiates this response. Despite dysregulated inflammasome activation being associated with disease severity, inflammasome activation, in addition to the interferon response was shown to play an important role in cell intrinsic antiviral responses.

We demonstrated that IL-1β, bolstered by epithelial-myeloid interactions, plays a crucial role in early antiviral defence against RSV, making inflammasome activation a double-edged sword. Given co-infections account for >30% of all respiratory viral infections, we explored the interactions between RSV and SARS-CoV-2. Our findings revealed bi-directional viral interference patterns, driven by time-dependent induction of type I interferons (IFNs), highlighting their underappreciated role in the airway epithelium's innate armoury. <br><br>By utilizing primary cell models, this work provides new insights into how the airway epithelium regulates innate immunity and highlights the complex balance between protective antiviral signalling and harmful inflammation during viral infection and co-infection.<br><br><i>Thesis is embargoed until 31 July 2027.</i><br>