Characterization of a novel nucleotide based second messenger system regulating innate immune responses

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The innate immune system is essential for the successful clearance of pathogens such as viruses and bacteria. It consists of a network including sensors and signaling cascades and leads to the synthesis of antiviral proteins and regulation of the immune system. Various ways evolved to transmit the signal from sensor proteins to downstream effector functions. These include direct protein-protein interactions and cytokines, which are protein based messenger molecules. An alternative way to transmit signals involves nucleotide-based messengers called "second messengers". Here I apply for funding to study a yet unappreciated novel signaling cascade that involves the activity of di-adenosine tetraphosphate (AP4A). AP4A stimulated human monocytes and murine bone marrow generate cytokines through a yet unstudied signaling cascade. Here I propose to study the generation of AP4A, the involved singalling cascade and the effects that AP4A has on an organismal level. We hypothesize that this mechanism is used to identify infected cells in tissue and to regulate the antiviral immune response.