Poster 49 Revisiting the innate immune response – a temporal resolution of whole blood stimulation Nico Reusch1,2, Sophie Müller1,2,3, Kevin Baßler1,4, Lorenzo Bonaguro1,2, Jonas Schulte-Schrepping1,2, Lukas Balsecivius1,2, Kilian Dahm1,2,5, Victoria Isakzai1,2, Theodore S. Kapellos1,2, Stefanie Warnat-Herresthal1,2, Charlotte Kröger1,2, Shobhit Agrawal1,2, Nora Balzer2,6, Tal Pecht1,2, Matthias Becker7, Patrick Günther2,4, Collins Osei-Sarpong8, Wataru Fujii1,2, Arik Horne1,2, Mohammad Lotfollahi9,10, Yuge Ji9,10, Erika Dudkin11, Humberto J. G. Ferreira12, Emily Hinkley12, Marc Beyer8, Kristian Händler12, Jan Hasenauer11, Rafael J. Argüello13, Fabian Theis9,10, Manfred Schmolz14, Anna C. Aschenbrenner1,15, Thomas Ulas1,2,12, Joachim L. Schultze1,2,12 1Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; 2Genomics & Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Germany; 3Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; 4Aimed analytics, Bonn, Germany; 5Translational Pediatrics, Department of Pediatrics, University Hospital Wuerzburg, 97080, Würzburg, Bavaria, Germany; 6West German Genome Center (WGGC), University of Bonn, Bonn, Germany; 7Modular High-Performance Computing and Artificial Intelligence, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.; 8Molecular Immunology in Neurodegeneration, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) and the University of Bonn, 53175 Bonn, Germany.; 9School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany, Department of Mathematics, Technical University of Munich, Munich. Germany; 10Helmholtz Center Munich – German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Munich, German; 11Computational Life Sciences, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany; 12Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and University of Bonn, Bonn, Germany; 13Aix Marseille University, CNRS, INSERM, CIML, Centre d’Immunologie de Marseille-Luminy, Marseille, France; 14HOT Screen GmbH, Reutlingen; 15Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands The immune system comprises various immune cell types with different effector functions. To prompt an effective and fine-tuned immune response to pathogens and other environmental stimuli, immune cells communicate through the release of signalling molecules and ligand-receptor interaction. Most studies only describe a snapshot of this dynamic process focussing on isolated cell types. To draw a more complete picture, we utilized a whole blood stimulation system to study the tran- scriptional dynamics of the immune response to lipopolysaccharide on a single cell level over seven time points. The myeloid and lymphoid compartment responded in waves of transcription to the LPS stimulation. The rapid release of type-1 inter- ferons by monocytes and dendritic cells triggered an interferon stimulated expres- sion program in T lymphocytes in the early phase after LPS stimulation. Strikingly, the blocking of this signaling abolished the activation of T lymphocytes and modified the activation profile of neutrophils highlighting the immunodulatory function of type-1 interferons in the context of LPS stimulation. Our results indicate that whole blood stimulation systems can be used dissect cellular communication such as paracrine type-1 IFN signaling between immune cells ex vivo, overcoming the limitations of analysing isolated cell types. We therefore propose a combination of whole blood culture systems with single-cell analysis to define the immune system’s reactivity in pathophysiological conditions and diseases. Systems Biology, Single-Cell Analysis Poster Session 2 155