BILITOLERANCE · Control of disease tolerance to infection by Biliverdin Reductase A

Control of disease tolerance to infection by Biliverdin Reductase A

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. While long recognized as a global unmet medical need, recent estimates revealed a far greater global health impact, in that sepsis accounts for 1 in 5 deaths worldwide. Protection from sepsis is classically attributed to the capacity of the host immune system to sense and clear pathogens. This is well illustrated by the overwhelming success of therapeutic approaches that mimic immune resistance mechanisms, such as vaccination or anti-microbial drugs and would suggest that resistance mechanisms are the only relevant defense strategy against infectious diseases. However, resistance mechanisms are not sufficient per se to prevent the pathogenesis of sepsis, as most sepsis patients succumb after pathogen elimination. An alternative view is that the pathogenesis of sepsis is driven by a dysregulated immune response, impairing organismal metabolism and leading to life-threatening organ dysfunction. In line with this, disease tolerance has recently emerged as an equally important defense strategy against infection, which aims at limiting damage to functions and structures imposed upon the host during infection, without exerting negative pressure on the pathogen. Recent studies have highlighted the real burden of severe infection and sepsis, showing that its impact is roughly double of what was previously thought, with 20% worldwide mortality being attributed to sepsis. The lack of specific therapies makes sepsis one of the most pressing unmet medical needs, further compounded by the rise of pathogen resistance to anti-microbial drugs. In fact, the need for alternative therapies to overcome rising antibiotic resistance has been highlighted by the World Health Organization as one of the main global health challenges currently faced by mankind. BILITOLERANCE aimed at the generation of basic and translational knowledge directly related to the role of BVRA in the establishment of disease tolerance in severe infection and sepsis. This should reveal new therapeutic targets against a broad range of infectious diseases, where the fast-paced rising threat of antibiotic resistance makes the modulation of disease tolerance an extremely attractive novel therapeutic strategy. The translational aspect of BILITOLERANCE bore the potential to directly decrease the rising disease burden of infectious diseases within the EU, and to generate important knowledge for academia as well as for clinical research and practice, with concrete benefits for the European economy and society in general.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз