Mechanisms of NET formation during sterile and bacterial inflammation

Principal investigators: Helena Block, Alexander Zarbock
Project number: CRC 1450 B05
Project term: 01/2021–12/2024

Graphical abstract
© CRC inSight

Upon activation at inflammatory sites, neutrophils release extracellular traps (NETs), being beneficial in infectious diseases, but rather detrimental during non-infectious diseases. To investigate this in detail, we will use intravital and ex vivo microscopy, whole-body imaging, and light sheet microscopy to analyze NET formation in the kidney during sterile inflammation, and in the lung during bacterial infection (1, 2). To further identify the implication of different signalling molecules, we will use knock-out or platelet-depleted mice to discriminate their contribution to NET formation (3, 4). Infecting mice with different S. aureus patient isolates will allow the analysis of NET degradation as evasion strategy (5). Using newly developed carbohydrate labelling and trackable disease markers will reveal the pathogeny of these bacterial strains.


Principal investigators

Project members


The names of the principal investigators in our network have been bolded. Publications released prior to 2021, when funding for our network commenced, represent previous project-related work.


Block H, Zarbock A. A Fragile Balance: Does Neutrophil Extracellular Trap Formation Drive Pulmonary Disease Progression?. Cells 2021;10Abstract
Masthoff M, Freppon FN, Zondler L, Wilken E, Wachsmuth L, Niemann S, Schwarz C, Fredrich I, Havlas A, Block H, Gerwing M, Helfen A, Heindel W, Zarbock A, Wildgruber M, Faber C. Resolving immune cells with patrolling behaviour by magnetic resonance time-lapse single cell tracking. EBioMedicine 2021;73: 103670. Abstract


Margraf A, Volmering S, Skupski J, Van Marck V, Makrigiannis AP, Block H, Zarbock A. The ITIM Domain-Containing NK Receptor Ly49Q Impacts Pulmonary Infection by Mediating Neutrophil Functions. J Immunol 2018;200: 4085-4093. Abstract


Block H, Stadtmann A, Riad D, Rossaint J, Sohlbach C, Germena G, Wu D, Simon SI, Ley K, Zarbock A. Gnb isoforms control a signaling pathway comprising Rac1, Plcbeta2, and Plcbeta3 leading to LFA-1 activation and neutrophil arrest in vivo. Blood 2016;127: 314-324. Abstract
Rossaint J, Kuhne K, Skupski J, Van Aken H, Looney MR, Hidalgo A, Zarbock A. Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response. Nat Commun 2016;7: 13464. Abstract
Volmering S, Block H, Boras M, Lowell CA, Zarbock A. The Neutrophil Btk Signalosome Regulates Integrin Activation during Sterile Inflammation. Immunity 2016;44: 73-87. Abstract


Herter JM, Kraft F, Van Aken H, Meersch M, Zarbock A, Rossaint J. GDF-15 prevents ventilator-induced lung injury by inhibiting the formation of platelet-neutrophil aggregates. Thromb Haemost 2015;114: 434-437. Abstract


Rossaint J, Herter JM, Van Aken H, Napirei M, Doring Y, Weber C, Soehnlein O, Zarbock A. Synchronized integrin engagement and chemokine activation is crucial in neutrophil extracellular trap-mediated sterile inflammation. Blood 2014;123: 2573-2584. Abstract
Sreeramkumar V, Adrover JM, Ballesteros I, Cuartero MI, Rossaint J, Bilbao I, Nacher M, Pitaval C, Radovanovic I, Fukui Y, McEver RP, Filippi M-D, Lizasoain I, Ruiz-Cabello J, Zarbock A, Moro MA, Hidalgo A. Neutrophils scan for activated platelets to initiate inflammation. Science 2014;346: 1234-1238. Abstract


Block H, Herter JM, Rossaint J, Stadtmann A, Kliche S, Lowell CA, Zarbock A. Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury. J Exp Med 2012;209: 407-421. Abstract
Ittner A, Block H, Reichel CA, Varjosalo M, Gehart H, Sumara G, Gstaiger M, Krombach F, Zarbock A, Ricci R. Regulation of PTEN activity by p38delta-PKD1 signaling in neutrophils confers inflammatory responses in the lung. J Exp Med 2012;209: 2229-2246. Abstract


Zarbock A, Singbartl K, Ley K. Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation. J Clin Invest 2006;116: 3211-3219. Abstract