Pathomechanisms that lead to the differentiation of dysfunctional dendritic cells during early polymikrobial sepsis

• Applicant: Professorin Dr. Stefanie Flohé
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2012 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 230022521

Sepsis is the response of the body to a systemic, mostly bacterial, infection and the most often cause of death on intensive care units. Septic patients often suffer from opportunistic infections due to the development of immunosuppression. Dendritic cells (DC) are antigen-presenting cells and orchestrate the immune response through their capacity to interact with diverse immune cells. Accordingly, DC play a pivotal role in the effective immune response to infections. Sepsis induces an altered differentiation of DC in the bone marrow through so far unknown mechanisms. Consequently, the function of newly generated DC is disturbed and the immune defense to microbes is impaired. The present study deals with the investigation of pathomechanisms that are responsible for the altered differentiation of DC and the associated enhanced susceptibility to secondary infections during sepsis. Therefore, a mouse model for septic peritonitis will be used. Additional infection with Pseudomonas aeruginosa will serve as model for an opportunistic infection.

• DFG Programme: Research Grants