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Role of the mitochondrial anti-viral signaling protein in sepsis

Final Report Summary - MAVS (Role of the mitochondrial anti-viral signaling protein in sepsis)

Severe sepsis is a life-threatening complication of infections and one of the major causes of morbidity and mortality. It is estimated, that approximately 600,000 cases of sepsis with more than 150,000 deaths occur annually in the European Union. To date, no approved pharmacologic therapies are available to fight sepsis and septic shock in human patients. These facts demonstrate the desperate need for a better understanding of the molecular and cellular pathophysiology of sepsis.
This project has investigated the acute inflammatory response during experimental sepsis in mice. The aims were focused on: 1) To investigate the role of the novel ‘mitochondrial anti-viral signaling protein’ (MAVS) during experimental bacterial sepsis. 2) To define the interactions of MAVS and the immune-modulatory cytokine, Interleukin-27 (IL-27). 3) To analyze the interactions of MAVS/IL-27 with the coagulation cascades during experimental sepsis.
The working program has included the establishment and maintenance of a breeding colony of MAVS-deficient mice at our institution. Major results are the detailed characterization of MAVS-deficient mice in polymicrobial sepsis, e.g. induced by cecal ligation and puncture including state-of-the-art molecular biology, immunology and imaging techniques.
The results of this project will be useful to deepen our understanding on the molecular mechanisms during sepsis and this could provide as solid basis for designing novel therapies against life-threatening sepsis. In future, the results may therefore be helpful to reduce deaths related to sepsis and confine the burden of sepsis on public health in countries of the European Union.
This project has been helpful for the research career development of the fellow, because it has provided resources to support his role as an independent investigator. The project has facilitated the reintegration of the fellow at the host institution.