Immune balance of the lung

由革兰氏阴性菌引起的肺部疾病是传染病死亡的主要原因。与有效治疗这些疾病相关的困难包括出现抗药性病原体、越来越多的老年人和免疫功能低下的患者。改善临床结果的一个有吸引力的目标是调节宿主肺免疫反应本身。然而，设计预防性或早期治疗干预措施以降低与肺损伤相关的死亡率的先决条件是了解肺内针对革兰氏阴性细菌及其原型产物脂多糖(内毒素)的先天免疫反应的作用。肺表面活性蛋白(SP)-A是肺天然免疫的主要分泌成分之一，对肺泡巨噬细胞具有重要的免疫调节作用，肺泡巨噬细胞是肺内主要的常驻免疫细胞。该计划将研究1)SP-A与内毒素结合的物理化学特征，2)参与SP-A对肺泡巨噬细胞的特异性作用的细胞表面和内体受体成分，以及3)SP-A诱导的负性调节因子在肺对内毒素的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.