Innate immune mechanisms and modulation during Salmonella infection (360G-Wellcome-102410_Z_13_A)

Respiratory infections, such as Respiratory Syncytial Virus (RSV) are a leading cause of morbidity and mortality worldwide, especially among the growing elderly population. Yet the impact of age-related changes in immunity in the lung remains insufficiently studied. In this project, we aim to establish an elderly murine model of RSV infection to studyhow aging alters anti-viral innate immune responses. Old (19-21 months) and young (2-3 months) C57BL/6 mice will be intranasally infected with the human RSV strain A2, and differences ininnate and adaptive immune responses characterised. We hypothesise that there are intrinsic differences in elderly alveolar macrophages, which determine how they respond to RSV and the outcome of infection, and we aim to identify key pathways that are altered in these cellswith age. Using this knowledge, we aim to manipulate the immune response in the elderly to reduce RSV-induced pathology. Finally, through collaboration with clinical colleagues, we will determine whether key mechanisms identified in the elderly mouse model, also differ in human infection in the elderly. Such studies will reveal novel insights into how the immune response to respiratory infection is altered in the elderly, aiding in the future development of new treatments andvaccines.