Endosomal signaling in innate immunity

• Applicant: Dr. Christina Moulakakis
• Subject Area: Pneumology, Thoracic Surgery
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 101947318

Emerging evidence demonstrates a pivotal role for the pulmonary collectin surfactant protein (SP)-A, a soluble pattern recognition receptor, in modulation of innate and adaptive lung immunity. SP-A induces the activation and immune responses of alveolar macrophages (AM), the most abundant immunocompetent cells in the alveolar space that form the first line of cellular defense. AM constitute the major route of removal of SP-A via the endolysosomal pathway. Endocytosis and signal transduction are indivisibly linked biological functions affecting the specificity of gene transcription and cell fate. A reciprocal link between endocytosis of and signaling by SP-A remain elusive. Significant SP-A turnover imbalances and impaired pulmonary defense are associated with numerous human pulmonary diseases, e.g. cystic fibrosis, respiratory distress syndrome, or viral/bacterial pneumonia. The endocytic pathway in AM could be targeted as an immune gateway for drug delivery using endosomal compartments as a storage device of therapeutic compounds whose release over time would help to improve or regain normal immune function. The planned project will investigate i) SPA endosomal signaling, ii) the IκB-α/ NF-κB signal transduction pathway in SP-A- and SPA/ SP-D-null mice.

• DFG Programme: Research Grants