Decoding the layers of tissue memory following respiratory virus infection

Immune memory explains the altered, often enhanced, response to secondary challenges. Historically, immune memory was thought to be an exclusive feature of the adaptive immune system. More recent studies, including our own, have begun to re-define immune memory as a much broader phenomenon affecting a wide range of cells including innate immune cells and epithelial cells. It remains unclear how memory in these different lineages is maintained and whether these cells cooperate to control re-infection more effectively. The main barrier to a deeper understanding of memory is that most studies examine individual cell lineages. Just as cognitive memory requires communication between many neurons, our over-arching hypothesis is that the most effective immune memory results from multiple cell lineages acting in concert. Addressing this hypothesis requires expertise across a range of cell lineages. We have assembled a team with complementary expertise in respiratory immunology to resolve this major gap and re-define immune memory. We will achieve this by: 1. Dissecting the memory responses to respiratory virus infection across space and time; 2. Investigating the cellular and molecular basis of immune memory networks; 3. Establishing how cell imprinting beyond the lung contributes to tissue memory.