Grant: CIHR Fellowship

Infection with influenza A viruses (IAV) causes inflammation in the lungs of infected individuals that is essential to clear the infection but that can also have detrimental effects if not well controlled. The restoration of lung tissue and return to homeostasis are critical to maintain efficient pulmonary function. Cells that contribute to inflammation are well characterized, however little is known about the ones that mediate lung repair. Furthermore, the mechanisms that govern the balance between inflammation and return to homeostasis are poorly understood. Innate lymphoid cells (ILC) represent an emerging population of cells that were recently identified and that can have a double-edged character, either by promoting a beneficial immune response or by causing detrimental immunopathological effects during IAV infection. However, the precise populations responsible for these phenomena are not well characterized and the mechanisms by which ILC are activated upon infection unknown. Here, we hypothesize that ILC populations act sequentially to promote inflammation, early upon infection and lung repair, at later stages. To test this, mice will be infected with IAV, and the ILC populations will be monitored daily. This will allow us to identify when ILC that promote inflammation or tissue repair accumulate in the lungs. Transfer experiments of these cells to mice at different time points post-infection will be performed to confirm the sequential effect of different ILC. Finally, ILC will be isolated from naive mice and stimulated in vitro to determine which stimulus is important for their activation and how they respond to it. There is a fine balance between inflammation, its resolution, and tissue repair. ILC can have both beneficial and detrimental effects in the lungs. A better understanding of ILC populations during IAV infection will provide new insights on the regulation of lung inflammation and could provide new therapeutics avenues.