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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Research Program

Pneumonia represents an enormous socioeconomic burden worldwide as well as a rising medical threat due to dramatically increasing rates of multi- and pan-drug resistant bacteria, and the emergence of viruses with pandemic potential. Thus, novel strategies against pneumonia are sorely needed. This unmet clinical need is directly addressed by the SFB TR84, which aims to decipher lung-specific molecular events and cellular interactions during infection and inflammation, with the goal of developing new therapeutic concepts against pneumonia.

The SFB-TR84 has established a tight-knit scientific network of highly recognized research teams currently comprising two medical departments, several basic science institutes, and three Max-Planck institutes. The high level of synergistic interaction between Gießen/Marburg and Berlin within the SFB-TR84 has been further strengthened by inclusion of 7 (previously 5) transregional projects (PIs from Gießen/Marburg). This interdisciplinary consortium is committed to comprehensively decipher the central role of the innate immune system for the pathogenesis of pneumonia. We will exploit these insights, derived from basic research as well as patient-derived observations for novel diagnostic, preventative and therapeutic strategies. The exact delineation of pathogen-host interactions and resulting infection and inflammation in a lung-specific context is the central mission of the SFB-TR84. This ambitious endeavour involves the development of new cutting-edge experimental techniques and concepts, such as dissecting cellular cross talks within the “alveolome” by state-of-the-art flow cytometric/imaging/genetic cell tracing techniques, assessment of the lung microbiome, the culture of lung spheroids or human lung tissue infected ex vivo, the utilization of vita-PAMPs for novel vaccination approaches, as well as innovative animal models (e.g. simulating respirator-related lung failure in pneumonia) and the identification of  candidate compounds for non-antibiotic based adjunctive therapies.

The SFB-TR84 will continue to focus on three key areas of pneumonia research.

Area A entitled “Pathogen recognition in the lung and initiation of innate immune response” investigates the recognition of pathogen-derived molecules by yet ill-defined pattern recognition receptors. The projects aim to delineate the function of such host sensors and their downstream pathways in the pulmonary innate immune response to infection. On the other hand, this area also addresses the role of microbial immune evasion strategies to avoid detection by host immune surveillance, or to manipulate innate immune signaling pathways. The gained insights will yield valuable new targets for therapeutic intervention. 

Area B entitled “Humoral and cell-based bronchoalveolar defence mechanisms” will address the role of local antimicrobial molecules such as peptidoglycan recognition proteins (PGLYRPs) and resident or newly recruited pulmonary immune cells in host defence, tissue damage, and repair. In addition, we will assess the impact of homeostasis alterations in infected lung cells on the innate immune response against respiratory pathogens.

Area C “Control of host response in the bronchoalveolar compartment and strategies for intervention”, will dissect the role of genetic regulatory events and cellular networks for site-specific temporal and spatial control of inflammatory responses, and delineate, molecular mechanisms underlying the often-observed detrimental break-down of local infection/inflammation containment (barrier failure). Finally, targeted manipulations of the innate immune response will be evaluated for treatment and prevention (e.g. vaccination) of pneumonia.

Potent cutting-edge microscopic techniques employed by the Z1 projects have provided essential support to almost all projects. The initial microscopic platforms and analysis tools have now been further advanced to the latest technological standards, opening new molecular imaging dimensions indispensable for nearly all projects in the next funding period.

As a result of its strong commitment to translational research, our interdisciplinary consortium has identified novel diagnostic (Ang1/Ang2) and therapeutic (e.g. aerosolized GM-CSF, recombinant adrenomedullin, resolvins) targets, which will be further evaluated in clinical studies run by the linked networks CAPNETZ (Community acquired pneumonia-network), PROGRESS (Pneumonia research network on genetic resistance and susceptibility for the evolution of severe sepsis) and German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL).