Forschungszentrum Borstel
Forschungszentrum Borstel

Priority Research Area Infections



The innate immune system provides a central protective barrier of human beings against bacterial infections. Bacterial membrane components are highly effective activators of innate immune responses such as inflammation and antimicrobial effector mechanisms. However, dysregulation of these immune resonses can lead to fatal diseases like sepsis, pneumonia and acute respiratory distress syndrome. The Division of Immunobiophysics investigates the molecular principles underlying the innate immune response to lipids and the specific mechanisms involved in the regulation of these pathways.


Main projects:

Cell activation by bacterial lipids

The characterization of structural and physical prerequisites for the inflammatory activity of bacterial lipids is the basis to elucidate the mechanisms by which lipids are recognized as danger signals by the immune system. The biological activity of lipids is based on the chemical composition and the organization of lipids in supramolecular membrane structures. We investigate natural and reconstituted model membranes and employ techniques such as fluorescence- and infrared spectroscopy for the biophysical characterization. We analyze the 3D organization of lipid membranes in solution by small angle X-Ray diffraction (SAXS) at the beamline P12 of the EMBL c/o DESY (Hamburg). Characterizing the structural and biophysical requirements for the inflammatory activity of bacterial pathogen factors provides us the information on the molecular mechanisms of the action of activators and inhibitors of the immunological response.

are of special importance in the recognition of lipids. The lipopolysaccharide (LPS)-binding protein (LBP) is the central regulator in the induction of immune responses to bacterial LPS in case of Gram-negative infections. LBP has a highly versatile biological functionality, which is not understood in many aspects. Thus, LBP is able to enhance and dampen inflammatory responses, the requirements for these opposing functions are only defined to a certain degree. In this context we are interested in the intercation of LBP with its ligand LPS, and secondary ligands such phospholipids and membranes.

Mechanisms of immune regulation in the lung

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. The pulmonary immune system is specifically adapted to microbial exposition by respiration. Our aim is to elucidate the lung specific mechanisms of regulating immune responses. To this aim we investigate the molecular principles of immune regulation by surfactant-proteins (surfactant-protein-A) and surfactant lipids. Both compound classes have potential for clinical applications i.e. to improve surfactant-substitution therapies in cases of bacterial induced pneumonia or pulmonary insufficiency such as acute respiratory distress syndrome. The approach of our group is to elucidate molecular interactions and mechanisms in membrane reconstitution models and in vitro tissue cell systems. Our aim is to provide the rationales for improving surfactant preparations for therapeutic immune modulation.

Peptide-based immune regulation (host-defense-peptides)

Antimicrobial peptides, also referred to as host-defense peptides are effector molecules of the innate immune system instrumental in the immune response to bacterial infection. This class of defense molecules is produced in all epithelial surfaces and in the lung. Besides their potent antimicrobial activity these peptides also have the potential to control immune cell functions, a property of importance in the regulation of over shooting immune responses such as sepsis or the resolution of chronic inflammatory diseases such as in COPD. Basis of this activity is among others a direct interaction of antimicrobial peptides with host cells (macrophages). Analysis of the mechanisms underlying antimicrobial peptide-based regulation of macrophage biology is essential to a targeted development of this class of immune response modifiers.