DC-ACTIVATION · Functional characterization of indirect dendritic cell activation and its impact on adaptive immunity

During infection, recognition of the infectious microorganism by the innate immune system leads to dendritic cell (DC) activation. This process is essential for the induction of antigen-specific adaptive immune responses. DC can be activated directly by conserved pathogen molecules or indirectly by inflammatory mediators released by other cell types that recognized such molecules. However, recent studies revealed that inflammation cannot completely substitute for direct DC recognition of microbes and that indirect DC activation is insufficient for immunologic priming. We will explore which aspects of DC activation are dependent on direct microbial priming by microarray comparison of directly and indirectly activated DC. The aim is to identify the critical signals that are necessary and sufficient to convert resting DC into immunostimulatory antigen presenting cells that are fully competent to prime T cell responses. Moreover, we will determine whether the same rules apply for pattern recognition receptors other than toll-like receptors. Finally, the fate of T cells primed by indirectly activated DC will be investigated. Particularly, we will evaluate whether these cells have acquired any signature indicative of regulatory properties. Understanding the signals that initiate and regulate DC activation is critical to our ability to manipulate the immune system for vaccination and therapy.