Sheza Farooq*

Division of Animal Biotechnology, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, Jammu and Kashmir, India

*Corresponding Author: Sheza Farooq, Division of Animal Biotechnology, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, Jammu and Kashmir, India.

Received: October 27, 2025; Published: December 31, 2025

Abstract

The formation of neutrophil extracellular traps (NETs) is a complex and fascinating phenomena that is crucial for understanding the way the innate immune system reacts to infections. Activated neutrophils release chromatin fibres and antimicrobial compounds during this process, forming a web-like structure that traps and immobilizes invasive microbes. NETs are a double-edged sword in host defense because their ability to entrap pathogens is balanced by the risk of tissue injury and autoimmune reactions. This article gives an overview of the molecular mechanisms behind NET formation, including the crucial role of reactive oxygen species (ROS), specific signalling pathways with emphasis on NET formation in various pathological conditions of animals and anti-TNF-α therapy.

Keywords: NETs; ROS; Anti-TNF-α; NETosis

References

1. Brinkmann Volker., et al. “Neutrophil extracellular traps kill bacteria”. Science5663 (2004): 1532-1535.
2. Kaplan Mariana J and Marko Radic. “Neutrophil extracellular traps: double-edged swords of innate immunity”. Journal of Immunology6 (2012): 2689-2695.
3. Vorobjeva NV and BV Chernyak. “NETosis: Molecular mechanisms, role in physiology and pathology”. Biokhimiia 85.10 (2020): 1178-1190.
4. Pilsczek Florian H., et al. “A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus”. Journal of Immunology12 (2010): 7413-7425.
5. Yipp Bryan G and Paul Kubes. “NETosis: How vital is it?”. Blood16 (2013): 2784-2794.
6. Metzler Kathleen D., et al. “Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity”. Blood3 (2011): 953-959.
7. Papayannopoulos Venizelos., et al. “Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps”. Journal of Cell Biology3 (2010): 677-691.
8. Fuchs Tobias A., et al. “Novel cell death program leads to neutrophil extracellular traps”. Journal of Cell Biology2 (2007): 231-241.
9. Stephan Alexander and Mario Fabri. “The NET, the trap and the pathogen: neutrophil extracellular traps in cutaneous immunity”. Experimental Dermatology3 (2015): 161-166.
10. Lin Andrew M., et al. “Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis”. Journal of Immunology1 (2011): 490-500.
11. Yost Christian C., et al. “Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates”. Blood25 (2009): 6419-6427.
12. Douda David N., et al. “Innate immune collectin surfactant protein d simultaneously binds both neutrophil 110 extracellular traps and carbohydrate ligands and promotes bacterial trapping”. Journal of Immunology4 (2011): 1856-1865.
13. Almyroudis Nikolaos G., et al. “NETosis and NADPH oxidase: at the intersection of host defense, inflammation, and injury”. Frontiers in Immunology 4 (2013): 45.
14. Halverson Tyler WR., et al. “DNA is an antimicrobial component of neutrophil extracellular traps”. PLOS Pathogens1 (2015): e1004593.
15. Richards RC., et al. “Histone H1: An antimicrobial protein of Atlantic salmon (Salmo salar)”. Biochemical and Biophysical Research Communications3 (2001): 549-555.
16. Papayannopoulos Venizelos., et al. “Neutrophil elastase enhances sputum solubilization in cystic fibrosis patients receiving DNase therapy”. PLOS One12 (2011): e28526.
17. Parker Heather., et al. “Requirements for NADPH oxidase and myeloperoxidase in neutrophil extracellular trap formation differ depending on the stimulus”. Journal of Leukocyte Biology4 (2012): 841-849.
18. Urban Constantin F., et al. “Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans”. PLOS Pathogens10 (2009): e1000639.
19. Sur Chowdhury Chanchal., et al. “Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: analysis of underlying signal transduction pathways and potential diagnostic utility”. Arthritis Research and Therapy3 (2014): R122.
20. Garcia-Romo Gina S., et al. “Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus”. Science Translational Medicine73 (2011): 73ra20.
21. Kessenbrock Kai., et al. “Netting neutrophils in autoimmune small-vessel vasculitis”. Nature Medicine6 (2009): 623-625.
22. Berthelot Jean-Marie., et al. “NETosis: At the crossroads of rheumatoid arthritis, lupus, and vasculitis”. Joint Bone Spine3 (2017): 255-262.
23. Szodoray Péter., et al. “Anti-citrullinated protein/peptide autoantibodies in association with genetic and environmental factors as indicators of disease outcome in rheumatoid arthritis”. Autoimmunity Reviews3 (2010): 140-143.
24. Dwivedi Nishant and Marko Radic. “Burning controversies in NETs and autoimmunity: the mysteries of cell death and autoimmune disease”. Autoimmunity6 (2018): 267-280.
25. Mendez Jonatan., et al. “Bovine neutrophils form extracellular traps in response to the gastrointestinal parasite Ostertagia ostertagi”. Scientific Reports1 (2018): 17598.
26. Lippolis John D., et al. “Neutrophil extracellular trap formation by bovine neutrophils is not inhibited by milk”. Veterinary Immunology and Immunopathology1-2 (2006): 248-255.
27. Grinberg Navit., et al. “β-hydroxybutyrate abrogates formation of bovine neutrophil extracellular traps and bactericidal activity against mammary pathogenic Escherichia coli”. Infection and Immunity6 (2008): 2802-2807.
28. Aulik Nicole A., et al. “Mannheimia haemolytica and its leukotoxin cause neutrophil extracellular trap formation by bovine neutrophils”. Infection and Immunity11 (2010): 4454-4466.
29. Jerjomiceva Natalja., et al. “Enrofloxacin enhances the formation of neutrophil extracellular traps in bovine granulocytes”. Journal of Innate Immunity5 (2014): 706-712.
30. Swain Dilip K., et al. “Formation of NET, phagocytic activity, surface architecture, apoptosis and expression of toll like receptors 2 and 4 (TLR2 and TLR4) in neutrophils of mastitic cows”. Veterinary Research Communications3 (2014): 209-219.
31. Villagra-Blanco Rodolfo., et al. “Bovine polymorphonuclear neutrophils cast neutrophil extracellular traps against the abortive parasite Neospora caninum”. Frontiers in Immunology 8 (2017): 606.
32. Karakurt Güneş and Kader Yildiz. “In vitro investigation of NETosis reaction developing from dog polymorphonuclear neutrophils to Toxoplasma gondii”. Turkish Journal of Veterinary and Animal Sciences4 (2020): 886-893.
33. Ciliberti Maria G., et al. “NETosis of peripheral neutrophils isolated from dairy cows fed olive pomace”. Frontiers in Veterinary Science 8 (2021): 626314.
34. Zhu Cheng-Long., et al. “PD-L1 maintains neutrophil extracellular traps release by inhibiting neutrophil autophagy in endotoxin-induced lung injury”. Frontiers in Immunology 13 (2022): 949217.
35. Marini Marco., et al. “TNF-αneutralization ameliorates the severity of murine Crohn's-like ileitis by abrogation of intestinal epithelial cell apoptosis”. Proceedings of the National Academy of Sciences of the United States of America14 (2003): 8366-8371.
36. Capsoni Franco., et al. “Effect of adalimumab on neutrophil function in patients with rheumatoid arthritis”. Arthritis Research and Therapy2 (2005): R250-R255.
37. Fossati Gianluca and Andrew M Nesbitt. “Effect of the anti-TNF agents, adalimumab, etanercept, infliximab, and certolizumab pegol (CDP870) on the induction of apoptosis in activated peripheral blood lymphocytes and monocytes”. American Journal of Gastroenterology 100 (2005): S298-S299.
38. Notebaert Sofie., et al. “NF-kappaB inhibition accelerates apoptosis of bovine neutrophils”. Veterinary Research2 (2005): 229-240.
39. Mukhopadhyay Srirupa, et al. “Role of TNFalpha in pulmonary pathophysiology”. Respiratory Research1 (2006): 125.
40. Pattacini Laura., et al. “Differential effects of anti-TNF-α drugs on fibroblast-like synoviocyte apoptosis”. Rheumatology3 (2010): 480-489.
41. Atreya Raja., et al. “Antibodies against tumor necrosis factor (TNF) induce T-cell apoptosis in patients with inflammatory bowel diseases via TNF receptor 2 and intestinal CD14+ macrophages”. Gastroenterology6 (2011): 2026-2038.
42. Billmeier Ulrike., et al. “Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases”. World Journal of Gastroenterology42 (2016): 9300-9313.
43. Zhang Cui., et al. “Anti-TNF-α therapy suppresses proinflammatory activities of mucosal neutrophils in inflammatory bowel disease”. Mediators of Inflammation (2018): 3021863.
44. Vomero M., et al. “Reduction of autophagy and increase in apoptosis correlates with a favorable clinical outcome in patients with rheumatoid arthritis treated with anti-TNF drugs”. Arthritis Research and Therapy1 (2019): 39.
45. Neuenfeldt Friederike., et al. “Inflammation induces pro-NETotic neutrophils via TNFR2 signaling”. Cell Reports3 (2022): 110710.

Citation

Citation: Sheza Farooq. “A Comprehensive Review on the Formation of Neutrophil Extracellular Traps in Animals". Acta Scientific Veterinary Sciences 7.12 (2025): 33-40.

Copyright

Copyright: © 2025 Sheza Farooq. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.