2026-10-13T06:20:12Z https://api.figshare.com/v2/oai

oai:figshare.com:article/32826344 2026-10-01T16:08:43Z portal_1172 item_type_8 month_year_10_2026

Inflammasomes and interferons: new insights into the innate immune response to RSV and SARS-CoV-2 infection in airway epithelial cells Erin M.P.E Getty (24304562) PUREID: 689206292 Respiratory viruses like RSV and SARS-CoV-2 pose significant public health threats, particularly to the young and elderly. Both viruses infect the airway epithelium, with severe disease associated with enhanced highly inflammatory immune responses. To develop novel therapeutics there is an urgent need to understand how specific innate immune responses are activated and regulated by RSV and SARS-CoV-2. Inflammasomes are cytosolic protein complexes that mediate the maturation and release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 and pyroptotic cell death. Given inflammasomes trigger potent inflammation that correlates with disease severity, we hypothesised that inflammasome activation may be critical. <br><br>Inflammasome research has focused primarily on myeloid cells and NLRP3, herein we investigated inflammasome signalling within the airway epithelium using physiologically relevant well-differentiated primary airway epithelial cell cultures (WD-PAECs). 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> 2026-10-01T16:08:43Z Text Thesis 10.17034/32826344.v1 https://figshare.com/articles/thesis/Inflammasomes_and_interferons_new_insights_into_the_innate_immune_response_to_RSV_and_SARS-CoV-2_infection_in_airway_epithelial_cells/32826344 All Rights Reserved Open Access after 2027-07-31