Migrating Platelets Are Mechano-scavengers that Collect and Bundle Bacteria

To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1016/j.cell.2017.11.001 Byline: Florian Gaertner [f.gaertner@med.uni-muenchen.de] (1,13,15,*), Zerkah Ahmad (1), Gerhild Rosenberger (1), Shuxia Fan (1), Leo Nicolai (1), Benjamin Busch (3), Gokce Yavuz (1), Manja Luckner (2), Hellen Ishikawa-Ankerhold (1), Roman Hennel (5), Alexandre Benechet (4), Michael Lorenz (1), Sue Chandraratne (1), Irene Schubert (1), Sebastian Helmer (1), Bianca Striednig (1), Konstantin Stark (1,13), Marek Janko (6), Ralph T. Bottcher (7,13), Admar Verschoor (8), Catherine Leon (9), Christian Gachet (9), Thomas Gudermann (10,13), Michael Mederos y Schnitzler (10,13), Zachary Pincus (11), Matteo Iannacone (4), Rainer Haas (3,14), Gerhard Wanner (2), Kirsten Lauber (5), Michael Sixt (12), Steffen Massberg [steffen.massberg@med.uni-muenchen.de] (1,13,**) Keywords platelets; cell migration; polarization; mechanosensing; methicillin-resistant S. aureus; neutrophils; NETosis; innate immunity; host-defense; sepsis Highlights * Platelets migrate at sites of vascular injury and inflammation * Platelets use mechanical force to scavenge substrate-bound particulate material * Migrating platelets use this ability to collect and bundle bacteria * Collection and bundling of bacteria facilitates neutrophil activation in sepsis Summary Blood platelets are critical for hemostasis and thrombosis and play diverse roles during immune responses. Despite these versatile tasks in mammalian biology, their skills on a cellular level are deemed limited, mainly consisting in rolling, adhesion, and aggregate formation. Here, we identify an unappreciated asset of platelets and show that adherent platelets use adhesion receptors to mechanically probe the adhesive substrate in their local microenvironment. When actomyosin-dependent traction forces overcome substrate resistance, platelets migrate and pile up the adhesive substrate together with any bound particulate material. They use this ability to act as cellular scavengers, scanning the vascular surface for potential invaders and collecting deposited bacteria. Microbe collection by migrating platelets boosts the activity of professional phagocytes, exacerbating inflammatory tissue injury in sepsis. This assigns platelets a central role in innate immune responses and identifies them as potential targets to dampen inflammatory tissue damage in clinical scenarios of severe systemic infection. Author Affiliation: (1) Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-Universitat, 81377 Munich, Germany (2) Ultrastructural Research, Department Biology I, Biozentrum, Ludwig-Maximillians-Universitat, 82152 Martinsried, Germany (3) Chair of Medical Microbiology and Hospital Epidemiology, Max von Pettenkofer Institute, Faculty of Medicine, LMU, 80336 Munich, Germany (4) Division of Immunology, Transplantation and Infectious Diseases, Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132 Milan, Italy (5) Department of Radiation Oncology, University Hospital, LMU Munich, 81377 Munich, Germany (6) Department of Materials Science, Technische Universitat, 64287 Darmstadt, Germany (7) Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany (8) Institute for Systemic Inflammation Research, Universitat zu Lubeck, 23538 Lubeck, Germany (9) UMR S949, Inserm, Universite de Strasbourgh, Etablissement Francais du Sang-Alsace, 67065 Strasbourg, France (10) Walther-Straub-Institut fur Pharmakologie und Toxikologie, Ludwig-Maximilians-Universitat, 80336 Munich, Germany (11) Department of Developmental Biology and Department of Genetics, Washington University, St. Louis, St. Louis, MO 63110, USA (12) Institute of Science and Technology (IST) Austria, 3400 Klosterneuburg, Austria (13) Deutsches Zentrum fur Herz-Kreislaufforschung (DZHK), 13347 Berlin, Germany (14) German Center for Infection Research (DZIF), Munich Site, 80336 Munich, Germany * Corresponding author Article History: Received 23 March 2017; Revised 27 August 2017; Accepted 30 October 2017 (miscellaneous) Published: November 30, 2017 (footnote)15 Lead Contact