Klaus Ruckdeschel
Prof. Dr. med.
Klaus Ruckdeschel
  • Research assistant
  • Head of research group
  • Medical specialist in Microbiology, Virology and Infectious Disease Epidemiology

The interaction of microbial pathogens with host cells critically determines the genesis of infectious diseases. When faced with a bacterial pathogen the multicellular organism raises a series of defense responses involving both innate and adaptive immunity. Professional phagocytes, such as neutrophils and resident macrophages, largely constitute the first line innate cellular host defense. They directly attack invading pathogens, mediate the secretion of pro-inflammatory cytokines and mount a protective immune response. Bacterial pathogens on the contrary have evolved sophisticated strategies for the evasion and neutralization of host defense mechanisms. A prototypical pathogen for the subversion of host immune responses is given by the gram-negative enteropathogenic bacterium Yersinia enterocolitica.

Our group is exploring the bidirectional crosstalk between Yersinia enterocolitica and its cellular host. Our studies aim to uncover the molecular mechanisms of Yersinia-mediated immunomodulation that enable the establishment of disease.

Funding

This work is supported by grants from the Deutsche Forschungsgemeinschaft DFG .

Projects

Modulation of host immune responses by Yersinia

Exploring the impact of Yersinia effector proteins on inflammatory and apoptotic signal transduction processesGram-negative, pathogenic bacteria from the genus Yersinia engage a type III protein secretion system that delivers a set of virulence proteins, the so-called Yops (Yersiniaouter proteins), inside eukaryotic cells. There, the Yops perturb key cellular signal transduction pathways of innate immunity. This renders infected cells unable to respond adequately to bacterial infection. The Yersinia Yops act at several cellular levels to suppress multiple programmed anti-bacterial effector functions. Accordingly, the Yop activities counteract phagocytosis, suppress pro-inflammatory activities and trigger apoptosis in macrophages.Our group is analyzing different molecular aspects in the crosstalk of Yersinia with host cells. We focus on the impact of Y. enterocolitica virulence traits on cellular signal transduction processes that are related to host defense mechanisms.In particular, the following issues are currently under investigation:

  • Regulation of apoptotic cell death in bacteria-infected macrophages
  • Deactivation of injected Yop proteins by the ubiquitin-proteasome pathway
  • Autophagic host defense responses in Yersinia infection
  • Subversion of pro-inflammatory signaling by Y. enterocolitica YopP

Wildtype strain photo black and white
Wildtype strain
Wildtype strain colored
Wildtype strain
Avirulent strain, phot black and white
Avirulent strain
Avirulent strain, photo colored
Avirulent strain

Yersinia-induced apoptosis

J774A.1 macrophages undergoing apoptosis 6 h after onset of Y. enterocoliticainfection.

Macrophages infected with the wild type strain display a heterogeneous, apoptotic morphology in phase-contrast microscopy (left). In a portion of the dying cells, apoptosis-typical DNA-fragmentation and nuclear condensation are detected by TUNEL-labeling of free DNA fragments with fluorescein (right). These apoptotic features are not observed in cells infected an avirulent Yersinia strain defective in type III secretion.

Staff • Group Ruckdeschel

Benjamin Berinson
Location

Campus Forschung N27 , 2nd Floor, Room number 02.027