Systems approaches for the study of immune signaling pathways have been traditionally based on selected purified cell types or cultured cell lines. However, in vivo responses involve the coordinated action of multiple cell types, which interact to establish an inflammatory microenvironment. Building on the approach and tools developed within the Milieu Interieur project, in particular whole blood TruCulture stimulations, we are interested to deconvolute dynamic immune responses to complex stimuli. More specifically this aims to identify the contribution of respective cell types, cellular receptors and downstream signaling pathways to an integrated immune response. To do this we are performing cellular assays with proteomic and transcriptomic readouts, combined with novel mathematical modeling.