Immune balance of the lung

由革兰氏阴性菌引起的肺部疾病是感染性疾病死亡的主要原因。与这些疾病的有效治疗相关的困难包括耐药性病原体的出现、老年个体和免疫功能低下患者的数量增加。改善临床结果的一个有吸引力的目标是调节宿主肺免疫应答本身。然而，设计预防性或早期治疗性干预措施以降低与肺损伤相关的死亡率的先决条件是理解肺中针对革兰氏阴性细菌及其原型产物脂多糖（LPS，内毒素）的先天免疫应答的作用。表面活性蛋白（SP）-A是肺先天免疫的主要分泌组分之一，其对构成肺的大多数常驻免疫细胞的肺泡巨噬细胞引发必需的免疫调节功能。计划中的项目将研究i）SP-A与LPS结合的物理化学特征，ii）参与SP-A对肺泡巨噬细胞特异性作用的细胞表面和内体受体组分，以及iii）SP-A诱导的负调节剂在肺特异性免疫反应中的作用。

Pulmonary diseases caused by Gram-negative bacteria are the leading cause of mortality from infectious diseases. The difficulties associated with effective treatment of these diseases include the emergence of antibiotic-resistant pathogens, increasing numbers of elderly individuals und immunocompromised patients. An attractive target for improving clinical outcomes is the modulation of the host pulmonary immune response itself. However, a prerequisite to designing prophylactic or early therapeutic interventions to reduce the mortality associated with lung injury is understanding the role of innate immune responses in the lung against Gram-negative bacteria and their prototypical product lipopolysaccharide (LPS, endotoxin). Surfactant protein (SP)-A is one of the primary secreted components of lung innate immunity eliciting essential immunomodulatory functions on alveolar macrophages which constitute the majority of resident immune cells of the lung. The planned project will investigate i) the physico-chemical characteristics of the binding of SP-A to LPS, ii) the cell surface and endosomal receptor components involved in the SP-A-specific effects on alveolar macrophages, and iii) the role of SP-A-induced negative regulators in the lung-specific immune reaction to LPS.