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，对医疗保健支出有相当大的影响。甲型流感病毒感染的一个显著特征是导致大量细胞凋亡，必须清除这些细胞以维持体内平衡。先天免疫系统的效应机制对识别和清除这些凋亡细胞至关重要。本研究的目的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，以及更一般地说，先天免疫系统如何调节肺部的炎症反应。这一建议的重点是甘露糖结合凝集素（MBL），一种先天性免疫系统的血清蛋白，不仅识别病原体，包括病毒，而且还识别改变的自我，如凋亡细胞。我们的初步数据表明：(1)缺乏MBL会损害肺中凋亡淋巴细胞的清除，肺是甲型流感病毒感染的主要器官；(2) MBL与凋亡淋巴细胞结合；(3) MBL在炎症调节中起关键作用。了解先天免疫系统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，将为治疗病毒感染并发症和其他可能的慢性肺部疾病提供新的治疗方法。

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.