Identification and characterization of the mechanisms of mast cell-mediated protection from bacterial skin wound infection by Pseudomonas aeruginosa

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Mast cells (MCs) have long been thought to be a dispensable cell type, which seemed only responsible for the annoying and sometimes even life threatening symptoms of allergic reactions. Over the last years, however, it became evident that MCs are also crucially important for optimal host defense against microbes, where they act as sentinels and effector cells of the innate immune responses. We and others have described that MCs are crucial to reduce morbidity and mortality of bacterial infections in mice. To further investigate the innate immune function of MCs in the defense of clinically relevant bacterial skin infections, we established a murine model of skin wound infection. By using this model we were able to demonstrate that MCs are essential for normal healing of infected wounds by controlling the bacterial burden. Here, we propose to identify the mechanisms and relevant signals that lead to an optimal MC function to defend bacterial skin infection. To this end, we will employ extensive in vitro and in vivo analyses to identify and characterize signals, which may ultimately lead to an improved host response against bacteria and will provide evidence that this principle is also effective in human skin. We therefore suggest a novel strategy for the treatment of bacterial infections in the skin, which will be assessed for efficacy in ex vivo models of bacterial skin infections. We hypothesize that such novel treatment strategies will provide a prophylactic approach to reduce the risk of bacterial infections in individuals with high risks of infections and an alternative therapeutic option to battle against bacteria resistant to common antimicrobial agents.