Forschungszentrum Borstel
Forschungszentrum Borstel

Priority Research Area Infections

Cellular Microbiology


We study aspects of host-pathogen interactions in tuberculosis and other infections with intracellular pathogens.

  • Intracellular survival mechanisms of mycobacteria.
  • Influence of nutrients (such as iron) and commensal bacteria on infection.
  • Interaction between cells of the innate and acquired immune system.
  • Pathways for presentation of mycobacterial antigens including lipids.
  • T cell activation and immune cell recruitment to the site of infection.

We bring together molecular immunology and cellular microbiology through experimental approaches on molecular, cellular, experimental animal model and human specimen levels to answer these questions. We hypothesize that the intracellular niche of mycobacteria and the microecology of the lung is pivotal to understand virulence and immunity in tuberculosis.

Fig. 1

Mycobacteria block phagosome maturation, which allows access to iron and secludes them from hostile lysosomes and antigen processing pathways. We found that mycobacteria enhance production of the lipid trehalose dimycolate (TDM) during intracellular growth. TDM decelerated phagosome maturation, but was inactivated in an interferon gamma (IFN-?) and inducible nitric oxide (NO) depending manner. NMR analysis revealed that NO altered the hydroxyl groups of the lipid suggesting their essentiality in virulence. Currently, the biophysics of the TDM-host membrane interaction is studied. Availability of certain essential nutrients is an important determinant for infection, generating competition between host and pathogen. Iron is an essential nutrient for mycobacteria. We study host genes involved in iron metabolism for their impact on tuberculosis. To directly measure iron in compartments and cells, we test fluorescent iron reporters for their eventual usage in the field. Nutritive competition is further complicated by other pathogenic as well as commensal bacteria, which appear more common in the lung then previously appreciated. We analyse different respiratory tract bacteria for their influence on nutritient availability and immunomodulation. We found that mice deficient for IL-18 are highly susceptible to M. tuberculosis due to biased immunity towards T helper 2 responses, i.e. reduced IFN-?, NO, alternatively activated macrophages, as well as interleukin 17/neutrophil driven pathology. The roles innate functions such as IL-18, neutrophils, NK cells and defensins in anti-mycobacterial immunity are currently investigated. We established a novel cross presentation pathway for T cell activation by mycobacteria, despite the phagosomal seclusion of mycobacteria, through apoptotic blebs from infected cells. Processing of antigens from apoptotic blebs requires functional lysosomes and saposins to break up the bleb membranes. We identified lysosomal phospholipases in macrophages involved in lipid antigen processing and degradation of phospholipids. Such enzymes are putatively involved in the break up of blebs, which is currently tested. Our studies aim to answer important questions in tuberculosis research including how the tubercle bacillus survives within host cells, which environment promotes or hampers mycobacterial growth and which immune mediators and antigen presentation pathways are essential for immune protection.