PPARα exacerbates necroptosis, leading to increased mortality in postinfluenza bacterial superinfection
Vincent C. Tam, Rosa Suen, Piper M. Treuting, Aaron M. Armando, Ronald Lucarelli, Norma Gorrochótegui-Escalante, Alan H. Diercks, Oswald Quehenberger, Edward A. Dennis, Alan Aderem, Elizabeth S. Gold
Abstract
Significance Superinfection with bacteria, such as Staphylococcus aureus, following influenza leads to increased morbidity and mortality compared to infection with either the bacteria or the virus alone. For example, secondary bacterial infections were responsible for a large percentage of the 50 million deaths caused by the 1918 influenza pandemic. The emergence of antibiotic-resistant strains has increased the threat of these bacteria commonly associated with influenza. We have determined that the increased mortality following superinfection is mediated, in part, by increased cell death in the lungs and have uncovered a molecular circuit that controls this process. A better understanding of the molecular regulation of immunity and cell death may enable the development of preventive and therapeutic treatments for bacterial superinfection.