Innate Immunity in the Clearance of Influenza A Virus Infected Apoptotic Cells

描述（由申请人提供）：流感感染是全球发病率和死亡率的主要原因之一，对医疗保健支出产生巨大影响。甲型流感病毒感染的一个显著特征是导致大量凋亡细胞，必须清除这些凋亡细胞以维持体内平衡。先天免疫系统的效应机制对于识别和去除这些凋亡细胞至关重要。该提案的目标是了解先天免疫系统如何促进甲型流感病毒感染诱导的凋亡细胞的清除，以及更普遍地了解先天免疫系统如何调节肺部的炎症反应。这项提案的重点是甘露糖结合凝集素（MBL），先天免疫系统的血清蛋白，不仅识别病原体，包括病毒，但也改变了自己，如凋亡细胞。我们的初步数据表明：（1）MBL的缺乏损害了肺（感染Infleunza A病毒的主要器官）中凋亡淋巴细胞的清除;（2）MBL与凋亡淋巴细胞结合;（3）MBL在炎症调节中起关键作用。了解先天性免疫系统在清除感染诱导的凋亡细胞和在清除凋亡细胞过程中调节炎症反应的分子方面，将为治疗病毒感染和其他慢性肺部疾病的并发症提供新的治疗方法。

Description (provided by applicant): 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.