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

先天免疫清除甲型流感病毒感染的凋亡细胞

• 批准号: 7392601
• 负责人: Kazue Takahashi
• 金额: $ 26.9万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-25 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7392601
• 关键词: Affect; Alveolar Cell; Alveolar Macrophages; Apoptosis; Apoptotic; Binding; Cells; Chronic lung disease; Complement; Data; Employee Strikes; Epithelial Cells; Excision; Goals; Healthcare; Homeostasis; Immune system; In Vitro; Infection; Inflammation; Inflammatory; Inflammatory Response; Influenza; Influenza A virus; Knockout Mice; Localized; Lung; Lymphocyte; Lymphocyte Count; Mannose Binding Lectin; Mannose-Binding Lectins; Matrix Metalloproteinases; Mediating; Molecular; Morbidity - disease rate; Natural Immunity; Numbers; Organ; Pattern Recognition; Phagocytosis; Play; Production; Role; Serum Proteins; System; Testing; Tissues; Virus; Virus Diseases; Wild Type Mouse; base; cell type; cytokine; in vivo; macrophage; mortality; novel therapeutics; pathogen; receptor; thymocyte; uptake; Affect; Alveolar Cell; Alveolar Macrophages; Apoptosis; Apoptotic; Binding; Cells; Chronic lung disease; Complement; Data; Employee Strikes; Epithelial Cells; Excision; Goals; Healthcare; Homeostasis; Immune system; In Vitro; Infection; Inflammation; Inflammatory; Inflammatory Response; Influenza; Influenza A virus; Knockout Mice; Localized; Lung; Lymphocyte; Lymphocyte Count; Mannose Binding Lectin; Mannose-Binding Lectins; Matrix Metalloproteinases; Mediating; Molecular; Morbidity - disease rate; Natural Immunity; Numbers; Organ; Pattern Recognition; Phagocytosis; Play; Production; Role; Serum Proteins; System; Testing; Tissues; Virus; Virus Diseases; Wild Type Mouse; base; cell type; cytokine; in vivo; macrophage; mortality; novel therapeutics; pathogen; receptor; thymocyte; uptake

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.

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，对医疗保健支出的影响很大。流感感染的一个引人注目的特征是导致的大量凋亡细胞，必须清除以维持稳态。先天免疫系统的效应器机制对于识别和去除这些凋亡细胞至关重要。该提案的目的是了解先天免疫系统如何促进流感A型流感病毒感染引起的凋亡细胞的清除，更广泛地说，先天免疫系统如何调节肺中的炎症反应。该提案的重点是甘露糖结合凝集素（MBL），这是一种先天免疫系统的血清蛋白，不仅识别包括病毒在内的病原体，而且还改变了自我改变，例如凋亡细胞。我们的初步数据表明，（1）缺乏MBL会损害肺中凋亡的淋巴细胞的去除，肺部是由Infleunza A病毒感染的主要器官； （2）MBL与凋亡淋巴细胞结合； （3）MBL在炎症的调节中起关键作用。了解先天免疫系统在清除感染引起的诱发细胞并调节凋亡细胞期间的炎症反应时，将提供新的治疗方法来治疗病毒感染并可能其他慢性肺部疾病。