Eva Pastille

Therapy of chronic immunosuppression after
polymicrobial sepsis

Polymicrobial sepsis is associated with the development of chronic immunosuppression leading to an enhanced susceptibility to secondary infections. This is based on the dysfunction of dendritic cells (DC) that is maintained even after resolution of the primary infection and is characterized by an impaired capacity of DC to secrete the Th1-polarizing cytokine IL-12 and to induce a protective Th1 cell response, while the production of IL-10 is enhanced. DC originate from precursors in the bone marrow. As the cause of the persistent DC dysfunction is still unknown, we want to investigate whether sepsis induces a defect in the differentiation of DC from progenitors in the bone marrow. In this project a mouse model of polymicrobial sepsis is used; the cecal ligation and puncture (CLP) model. When mice recovered from sepsis, the differentiation of DC from the bone marrow is analyzed in vitro and the mechanisms underlying the DC mediated inhibition of Th cell responses are examined. Furthermore, the involvement of Natural killer cells in the Th cell inhibition is characterized. To test which cell population favors the differentiation of dysfunctional DC, the bone marrow of septic mice is modified. The aim of the project is the restoration of DC function to facilitate an effective immune response towards secondary infections.

1st supervisor: Dr. Stefanie B. Flohé
2nd supervisor: Prof. Dr. med. Jan Buer

Institute:
Surgical Research, Department of Trauma Surgery, University Hospital Essen, University of Duisburg-Essen

Telephone: +49 (0)201 - 723 - 4548
E-mail: e.pastille@arcor.de