Alveolar macrophages regulate the susceptibility of alveolar epithelial cells to influenza A virus infection and the outcome of infection. (P4241)

Abstract Influenza A virus (IAV) is a major human pathogen. Patients with lethal primary influenza pneumonia exhibit severe diffuse lung inflammation, respiratory tract injury, and diffuse alveolar damage. While IAV is cytolytic, the host immune response has recently been appreciated to also be a significant cause of lung injury during IAV infections. To explore the role of alveolar macrophages (AMs) in virus clearance and lung injury/repair during IAV infection, we developed a novel mutant mouse strain with a selective deficiency in the AM compartment. We found that AM deficient mice die following a sub-lethal (in control mice) IAV infection in spite of a normal immune response and virus clearance. However, these mice undergo a rapid decline in O2 saturation at the onset of the adaptive immune response (5-6 dpi) and also demonstrate an increased susceptibility of alveolar type I epithelial cells to IAV infection. Destruction of this critical cell type necessary for oxygen exchange by virus or the adaptive response likely accounts for their loss of lung function and death. Thus AMs may have a critical function in controlling the susceptibility of alveolar epithelial cells to IAV infection and therefore the severity of infection.