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oai:figshare.com:article/32826221 2026-10-01T16:09:49Z portal_1172 item_type_8 month_year_10_2026

Airway epithelium and respiratory syncytial virus - effect of developmental age on responses to infection Mary McCabe (24304487) PUREID: 668993707 Virus respiratory syncytial virus innate immunity innate immune response infant interferon knowledge graph interferon epsilon ISG15 text mining Respiratory syncytial virus (RSV) remains a significant global health concern, particularly among vulnerable populations, such as infants and older adults, who experience the greatest burden of severe disease. Despite advances in vaccine development and monoclonal antibody prophylaxis, understanding the immune determinants underlying severe RSV disease remains incomplete. The disease is primarily driven by a dysregulated host immune response, yet the immune mechanisms involved, particularly in early-life, are still poorly understood. In this thesis, we focused on the role of innate immune responses in RSV infection, particularly during early life. Using well-differentiated paediatric nasal epithelial cell (WD-PNEC) cultures from newborns and one-year-olds, we demonstrated that innate immune responses to RSV become more robust with age, with significant differences in cytokine secretion and interferon-stimulated gene (ISG) expression between newborns and the same children at one-year-old. This work highlights the crucial role of the airway epithelium in the early immune response to RSV, which is a key factor in determining disease severity. Notably, interferon epsilon (IFNε), a lesser-characterized type I IFN, is expressed at lower levels in newborns, which may contribute to their increased susceptibility to severe disease. Further investigation of interferon-stimulated gene 15 (ISG15), an immune modulator highly expressed during RSV infection, revealed that although ISG15 knockout modestly reduced RSV spread, it did not significantly impact infectious viral release. These findings suggested that ISG15 may not be directly antiviral but could influence infection outcomes through modulation of interferon signalling. This work provides critical insights into the complex interplay of immune responses during RSV infection, emphasizing the importance of early-life immunity and offering potential avenues for therapeutic interventions aimed at enhancing innate immune responses to reduce disease severity. Thesis is embargoed until 31 July 2027. 2026-10-01T16:09:49Z Text Thesis 10.17034/32826221.v1 https://figshare.com/articles/thesis/Airway_epithelium_and_respiratory_syncytial_virus_-_effect_of_developmental_age_on_responses_to_infection/32826221 All Rights Reserved Open Access after 2027-07-31