Transregional Collaborative Research Center SFB-TR 84 - “Innate Immunity of the Lung: Mechanisms of Pathogen Attack and Host Defence in Pneumonia“

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Area C

Control of host response in the bronchoalveolar compartment and strategies of intervention

 

Area C is dedicated to important mechanisms of controlling and limiting pulmonary inflammation, and the testing of innovative intervention procedures.
Project C01 (Schmeck/Vingron) will test the hypothesis that the innate immune responses against L. pneumophila infection in the alveolar compartment is critically mediated by microvesicle-packed small RNAs of bacterial and host origin by experimental and bioinformatics approaches. By using complex, clinically relevant mouse models, project C03 (Mayer/Witzenrath) will analyse the role of 18R-HEPE and RvE1 during induction and resolution of inflammation in pneumonia, and aims to develop new adjunctive therapeutic strategies in pneumonia. Project C06 (Witzenrath/Weissmann) studies the regulation of the Ang-1/2 and Tie-2 system, addresses the role of Ang-1 in new infection models by using newly established transgenic mice and transfers important findings to the human system. Project C07 (Fischer/Müller-Redetzky) will elucidate the role of host-derived extracellular nucleic acid DAMPs (eRNA and NETs) and of natural antagonists in S.p. pneumonia, aiming to interfere with the deleterious effects of these factors by using adrenomedullin to improve pneumonia outcome. Combining their complimentary expertise in carbohydrate chemistry / vaccinology and infection immunology, the teams in project C08 (Seeberger/Sander) will develop a new generation of fully synthetic, highly efficacious vaccines and test their efficacy against two major respiratory bacterial pathogens.

Abbreviations: B/Gi-M, Berlin/Gießen-Marburg; B, Berlin; Gi-M, Gießen-Marburg; miRNA, microRNA; sRNA, short RNA; L.p., Legionella pneumophila; MØ, macrophage; 18R-HEPE, 18(R)-Hydroxyeicosa-5Z,8Z,11E,14Z,16E-pentaenoate; RvE1, resolvin E1; Ang, angiopoietin; VT, vasculotide (synthetic Tie-2 ligand); S.a., Staphylococcus aureus; eRNA, extracellular RNA; Mono, monocyte; AM, adrenomedullin; NETs, neutrophil extracellular traps; polySia, polysialic acid; K.p., Klebsiella pneumonia; TH1, T helper 1; TFH, T follicular helper cells; APC, antigen presenting cell; SP3tetra, synthetic tetrasaccharide from S.p. capsule; Vita-PAMP, viability-associated PAMP; EC, endothelial cell; AECs, alveolar epithelial cells.