Background and previous work Microglia are major players of the innate immune system in the brain. Our ongoing work revealed the signalling protein PI3Kgamma as a key mediator of microglia functions. We have shown that microglial phagocytosis, migration, proliferation and cytokine release are controlled by defined signalling activities of PI3Kgamma. Stimulation of these functions by increasing doses of endotoxins partially revealed hormetic reaction pattern mediated by PI3Kgamma.
Specific aims and working programme Based on of these recent data we hypothesise crucial regulatory functions of PI3Kgamma in enduring resistance or persistence responses of microglia at increasing doses of pathogen- or damage- associated factors. In line with our recent work and inspired by a recent evidences about dose dependent induction of "training" or "tolerance" effects of microbial pathogens on monocytes our project is aimed to analyse PI3Kgamma related signalling processes involved in microglia adaptive responses.