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A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeutics

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Activated neutrophils release neutrophil extracellular traps (NETs) in response to a variety of stimuli. NETosis is driven by protein-arginine deiminase type 4, with the release of intracellular granule components that function by capturing and destroying microbes, including viral, fungal, bacterial, and protozoal pathogens. The positive effects of pathogen control are countered by pro-inflammatory effects as demonstrated in a variety of diseases. Components of NETS are non-specific, and other than controlling microbes, they cause injury to surrounding tissue by themselves or by increasing the pro-inflammatory response. NETs can play a role in enhancement of the inflammation seen in autoimmune diseases including psoriasis, rheumatoid arthritis, and systemic lupus erythematosis. In addition, autoinflammatory diseases such as gout have been associated with NETosis. Inhibition of NETs may decrease the severity of many diseases improving survival. Herein, we describe NETosis in different diseases focusing on the detrimental effect of NETs and outline possible therapeutics that can be used to mitigate netosis. There is a need for more studies and clinical trials on these and other compounds that could prevent or destroy NETs, thereby decreasing damage to patients.

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Funding

This publication was supported by funds from USDA NIFA, grant no. 2016-11003, awarded to Laurel Gershwin and UC Davis Comparative Medical Science Training Program (NIH grant no.: T32 OD011147).

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  1. Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California Davis, 1 Shields Ave, Davis, CA, USA

    Victoria Mutua & Laurel J. Gershwin

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Victoria Mutua researched and wrote the review. Laurel Gershwin provided edits to the first draft and advice on the review composition.

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Mutua, V., Gershwin, L.J. A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeutics. Clinic Rev Allerg Immunol 61, 194–211 (2021). https://doi.org/10.1007/s12016-020-08804-7

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