Modification of host defense mechanisms in severe bacterial infectious diseases

• Applicant: Dr. Sonja Oehmcke-Hecht
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2011 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 201106193

The aim of my application is to identify important so-called host effector systems that are targeted during invasive and life-threatening bacterial infection and study their activation/modulation by bacterial pathogens. My previous work has shown that systemic activation of the contact system in a murine sepsis model evokes severe complications, including lung damage of the infected mice, and eventually contributes to a fatal outcome. By looking at the molecular mechanisms that trigger contact system activation, I found that in addition to bacteria also neutrophil extracellular traps (NETs) and microparticles serves as an activating surface for the contact system. These findings have major patho-physiologic consequences as my data clearly show that the activation of the contact system stabilizes a formed clot. Notably, depletion of contact factors is often seen in septic patients and this may lead to the formation of unstable clots. This in turn may lead to the release of microthrombi into the circulation and contribute to severe hemostatic complications such as disseminated intravascular coagulation, which is associated with high mortality. The research projects presented in this application will address this important clinical problem. I intend to characterize microparticles in sepsis, by performing ex vivo as well as in vivo models and analyze patient material, since they are released into the circulation and will therefore present an ideal surface triggering a systemic activation of the contact system.

• DFG Programme: Research Grants