Influenza infection is one of the leading causes of morbidity and mortality worldwide, with a commensurately large impact on healthcare spending. A striking feature of influenza A viral infection is the large number of apoptotic cells that result and which must be cleared in order to maintain homeostasis. The effector mechanisms of the innate immune system are critical to the recognition and removal of these apoptotic cells. The goal of this proposal is understanding how the innate immune system facilitates clearance of influenza A virus infection-induced apoptotic cells, and more generally how the innate immune system modulates the inflammatory response in the lungs. The focus of this proposal is mannose-binding lectin (MBL), a serum protein of the innate immune system that recognizes not only pathogens, including viruses, but also altered self, such as apoptotic cells. Our preliminary data indicate that (1) Lack of MBL impairs removal of apoptotic lymphocytes in lungs, the primary organ infected by infleunza A virus; (2) MBL binds to apoptotic lymphocytes; and (3) MBL plays a key role in the modulation of inflammation. Understanding the molecular aspects of the innate immunte system in clearing infection-induced aoptotic cells and regulating the inflammatory response during the removal of apoptotic cells will provide new therapeutic approaches to treat complications from virus infection and likely other chronic lung diseases. ? ? ?
