Immune balance of the lung

点击翻译按钮获取中文摘要

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.