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.


Ji Y, Chakraborty T, Wegner SV. Self-Regulated and Bidirectional Communication in Synthetic Cell Communities. ACS Nano 2023;17: 8992-9002. Abstract
Ludwig N, Thörner-van Almsick J, Mersmann S, Bardel B, Niemann S, Chasan AI, Schäfers M, Margraf A, Rossaint J, Kahl BC, Zarbock A, Block H. Nuclease activity and protein A release of Staphylococcus aureus clinical isolates determine the virulence in a murine model of acute lung infection. Front. Immunol. 2023;14Abstract


Block H, Rossaint J, Zarbock A. The Fatal Circle of NETs and NET-Associated DAMPs Contributing to Organ Dysfunction. Cells 2022;11Abstract
Conrad C, Yildiz D, Cleary SJ, Margraf A, Cook L, Schlomann U, Panaretou B, Bowser JL, Karmouty-Quintana H, Li J, Berg NK, Martin SC, Aljohmani A, Moussavi-Harami SF, Wang KM, Tian JJ, Magnen M, Valet C, Qiu L, Singer JP, Eltzschig HK, Bertrams W, Herold S, Suttorp N, Schmeck B, Ball ZT, Zarbock A, Looney MR, Bartsch JW. ADAM8 signaling drives neutrophil migration and ARDS severity. JCI Insight 2022;7Abstract


Block H, Zarbock A. A Fragile Balance: Does Neutrophil Extracellular Trap Formation Drive Pulmonary Disease Progression?. Cells 2021;10Abstract
Chakraborty T, Wegner SV. Cell to Cell Signaling through Light in Artificial Cell Communities: Glowing Predator Lures Prey. ACS Nano 2021;15: 9434-9444. Abstract
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
Rossaint J, Thomas K, Mersmann S, Skupski J, Margraf A, Tekath T, Jouvene CC, Dalli J, Hidalgo A, Meuth SG, Soehnlein O, Zarbock A. Platelets orchestrate the resolution of pulmonary inflammation in mice by T reg cell repositioning and macrophage education. J Exp Med 2021;218: e20201353. Abstract


Hoste EAJ, Kellum JA, Selby NM, Zarbock A, Palevsky PM, Bagshaw SM, Goldstein SL, Cerda J, Chawla LS. Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol 2018;14: 607-625. 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


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


Rossaint J, Spelten O, Kassens N, Mueller H, Van Aken HK, Singbartl K, Zarbock A. Acute loss of renal function attenuates slow leukocyte rolling and transmigration by interfering with intracellular signaling. Kidney Int 2011;80: 493-503. Abstract


Zarbock A, Schmolke M, Spieker T, Jurk K, Van Aken H, Singbartl K. Acute uremia but not renal inflammation attenuates aseptic acute lung injury: a critical role for uremic neutrophils. J Am Soc Nephrol 2006;17: 3124-3131. Abstract