TRR 84:  Innate Immunity of the Lung: Mechanisms of Pathogen Attack and Host Defence in Pneumonia

• Subject Area: Medicine
• Term: from 2010 to 2022
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 114933180

“The emergence of respiratory viruses with pandemic potential poses a rising medical threat” – We had made this statement in our SFB-TR84-proposal in 2017! In 2019, a new zoonotic, respiratory tract and lung infection caused by SARS-CoV-2 emerged in Wuhan, China, leading to a pandemic with unpredicted health and socio-economic impact worldwide. Since 2010, the SFB-TR84, which is now in its 3rd funding period, aims to decipher lungspecific mechanisms and cellular interactions during infection and inflammation, with the goal of developing new therapeutic concepts for the treatment of pneumonia. The SFB-TR84 has established a tightly woven scientific network of highly recognized research teams comprising four medical departments, several basic science institutes, the Robert-Kochinstitute and two Max-Planck institutes. The scientific objectives of the SFB, its staffing, its high methodological-analytical competence and a decade of collaboration provide an excellent basis for rapid and consistent research on COVID-19. Indeed, the SFB members already contributed publications analysing different aspects of SARS-CoV-2 and COVID-19, including highimpact journals (with SFB-TR84 funding: e.g. published: 1 x Cell, 2 x Nature, 1 x Nat. Biotech., and 1 x Cell “accepted”) within the first 9 months after emergence of the disease. We therefore apply for funding of a “COVID-19 extra-year” of the SFB-TR84 to use our established research consortium to decipher fundamental aspects of COVID-19 thereby contributing to the global fight against COVID-19. We feel that this will significantly drive SARS-CoV-2/COVID-19 research in Germany, as many key players currently managing this pandemic at the virological, clinical and epidemiological level are part of this SFB. The competence ranges from basic SARS-CoV-2 virology to molecular principles of human SARS-CoV-2 infection and host defense and to identification of new therapeutic targets. Funding this research within an “additional COVID-19 year” by the DFG will help rapidly to gain the urgently needed knowledge on virus-host interactions and pathomechanisms of disease, including the immune responses. This knowledge is crucial for developing vaccines and therapeutics against COVID-19 to limit further global spread of the virus ultimately.

• DFG Programme: CRC/Transregios

Completed projects

• A01 - Antiviral IFNs and NK cells in COVID-19 (Project Heads Bauer, Stefan ;  Diefenbach, Andreas ;  Opitz, Bastian )
• A02 - FXII – between hypercoagulation and fibrinolysis shutdown in COVID-19 (Project Heads Hackstein, Holger ;  Kübler, Wolfgang ;  Preissner, Klaus T. ;  Wygrecka, Malgorzata )
• A04 - Role of ER stress in SARS-CoV-2 lung infection (Project Heads Abu Mraheil, Mobarak ;  Chakraborty, Trinad ;  Hippenstiel, Stefan ;  Pillich, Helena )
• A05 - Impact of the gut and upper respiratory tract microbiota on the course of COVID-19 and the proinflammatory immune response (Project Heads Chaput, Catherine ;  Heimesaat, Markus M. ;  Opitz, Bastian )
• A06 - Pathogen recognition by taste and odorant receptors and coupling to BALT formation and epithelial remodeling (Project Heads Diefenbach, Andreas ;  Krasteva-Christ, Gabriela ;  Kummer, Wolfgang )
• A07 - Characterization of SARS-CoV-2 isolates and functional studies of viral virulence in human lung organoids (Project Heads Drosten, Christian ;  Hönzke, Katja ;  Zscheppang, Katja )
• B01 - Peptidoglycan recognition proteins (PGLYRPs) as regulators of innate immunity in the lung (Project Heads Aly, Sahar ;  Hain, Torsten ;  N´Guessan, Dje Philippe ;  Suttorp, Norbert ;  Zahlten, Janine )
• B02 - AAV-vector containing SARS-CoV-2 S receptor binding domain (AAV-SRBD) as a potential vaccine candidate (Project Heads Herold, Ph.D., Susanne Valerie ;  Peteranderl, Ph.D., Christin ;  Pleschka, Stephan ;  Wolff, Thorsten )
• B03 - Development and function of respiratory macrophages and dendritic cell subsets during bacterial pneumonia (Project Heads Bauer, Stefan ;  Hackstein, Holger ;  Lohmeyer, Jürgen )
• B04 - Novel pathways of neutrophil-endothelial cell interaction in acute bacterial pneumonia: impact on transmigration kinetics and organ failure (Project Heads Santoso, Sentot ;  Schermuly, Ralph )
• B05 - Paralysis of pulmonary immunity after cerebral ischemia by parasympathetic nervous system (Project Heads Meisel, Andreas ;  Meisel, Christian Alexander ;  Volk, Hans-Dieter )
• B06 - Role of human alveolar macrophages in SARS-CoV-2 infection (Project Heads Antelmann, Haike ;  Hippenstiel, Stefan ;  Hocke, Andreas )
• B08 - Therapeutic targeting of altered airway microbiota to prevent lung damage and pneumonia in mice with cystic fibrosis-like lung disease (Project Heads Hain, Torsten ;  Mall, Marcus )
• B09 - Mononuclear phagocyte differentiation trajectories driving a cytokine storm and tissue damage in COVID-19 (Project Heads Herold, Ph.D., Susanne Valerie ;  Triantafyllopoulou, Antigoni )
• C01 - Outer membrane vesicles in SARS-CoV2-bacteria co-infection (Project Heads Marsico, Annalisa ;  Schmeck, Bernd ;  Vingron, Martin )
• C02 - Krüppel-like factors as regulators of inflammation in pneumococcal pneumonia (Project Heads Hippenstiel, Stefan ;  Lohmeyer, Jürgen )
• C03 - Resolvin E1 and related lipid mediators programming the resolution of inflammation in pneumonia (Project Heads Mayer, Konstantin ;  Witzenrath, Martin )
• C04 - Pathogen induced alterations of the Ubiquitin-Proteasome-System (UPS) during the Innate Immune Response in the Lung (Project Heads Kloetzel, Peter Michael ;  Seifert, Ulrike )
• C05 - Interference of S. pneumoniae and L. pneumophila with glucocorticoid dependent signalling in pulmonary cells and human lungs (Project Heads Hippenstiel, Stefan ;  Hocke, Andreas )
• C06 - Lung protection in severe COVID-19 by means of Tie2 agonism (Project Heads Weißmann, Norbert ;  Witzenrath, Martin )
• C07 - Host extracellular nucleic acids as DAMPs in severe pneumococcal pneumonia: Pathogenetic mechanisms and therapeutic approaches in combination with adrenomedullin (Project Heads Fischer, Silvia ;  Müller-Redetzky, Holger )
• C08 - Investigating immunological cross-reactivities to SARS-CoV-2 (Project Heads Sander, Leif Erik ;  Seeberger, Peter H. )
• C09 - Protective effect of CFTR modulators on endothelial barrier failure in COVID-19 induced ARDS (Project Heads Kübler, Wolfgang ;  Suttorp, Norbert ;  Witzenrath, Martin )
• C10 - Dissecting the role of RNA in host defence and immune-subversion by SARS-CoV-2 (Project Heads Bauer, Stefan ;  Sander, Leif Erik ;  Schulte, Leon )
• T01 - Fabrication and culture of high-precision native tissue slices produced by high-pressure water jet cutting for long-term intravital microscopy based analysis of innate immune mechanisms of human lung (Project Heads Hassel, Thomas ;  Hippenstiel, Stefan ;  Hocke, Andreas )
• Z01 - High-end microscopy and digital image analysis to depict pathogenesis of COVID-19 (Project Head Hocke, Andreas )
• Z01 - Experimental pathology and in vivo-modelling of SARS-CoV-2 infection in different hamster species (Project Heads Gruber, Ph.D., Achim Dieter ;  Trimpert, Jakob )
• Z02 - Management and Coordination (Project Head Suttorp, Norbert )

• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Co-Applicant Institution: Freie Universität Berlin; Humboldt-Universität zu Berlin; Justus-Liebig-Universität Gießen; Philipps-Universität Marburg
• Participating University: Friedrich-Alexander-Universität Erlangen-Nürnberg
• Spokesperson: Professor Dr. Norbert Suttorp