Neutrophil Extracellular Trap Dynamics in Viral Infections

Neutrophil extracellular traps (NETs) are web-like assemblies of decondensed chromatin and granular proteins expelled by neutrophils in response to a variety of stimuli, including viral pathogens. NET formation, or NETosis, serves both protective and pathological roles: these structures can immobilise and neutralise virions but may also exacerbate tissue damage, vascular leakage and thrombosis. Viral engagement of pattern‐recognition receptors triggers intracellular signalling cascades involving reactive oxygen species, peptidylarginine deiminase 4 (PAD4) and membrane pore-forming proteins such as gasdermin D, culminating in chromatin decondensation and release. The balance between effective antiviral defence and uncontrolled inflammatory injury is shaped by viral species, host genetics and the timing and magnitude of neutrophil recruitment. In respiratory infections, excessive NET accumulation correlates with acute lung injury, whereas insufficient early NET release can permit viral dissemination. Understanding the regulatory checkpoints of NET dynamics is essential for devising interventions that preserve antiviral efficacy while mitigating collateral damage.

Research from Nature Portfolio

Recent studies have illuminated mechanisms by which NETs influence the course of viral pneumonia. Work on influenza virus infection has revealed that gasdermin D amplifies lung neutrophil responses, driving NET release and downstream inflammation; genetic ablation of gasdermin D attenuates weight loss, histopathology and mortality without altering viral load, highlighting a therapeutic axis. Complementary evidence from severe influenza cohorts demonstrates that elevated NET formation, delayed neutrophil apoptosis and heightened protease activity predict poor clinical outcomes, underscoring NET-related signatures as prognostic biomarkers. Foundational research into respiratory syncytial virus has further characterised classic ROS-dependent NETosis mediated by PAD4 and necroptotic pathways, revealing receptor and kinase dependencies that may be exploited to temper immunopathology in paediatric bronchiolitis.

Neutrophil Extracellular Trap Dynamics in Viral Infections publication trend

The graph below shows the total number of articles in neutrophil extracellular trap dynamics in viral infections across all publications each year (not limited to Nature Index journals).

Technical terms

Neutrophil Extracellular Traps (NETs): Meshes of DNA and neutrophil‐derived proteins expelled to trap pathogens.

NETosis: Regulated cell death or activation programme leading to NET release.

Gasdermin D (GSDMD): Pore-forming protein that mediates membrane permeabilisation and facilitates NETosis.

Peptidylarginine deiminase 4 (PAD4): Enzyme that citrullinates histones, promoting chromatin decondensation in NET formation.

Reactive Oxygen Species (ROS): Chemically reactive molecules generated by NADPH oxidase that trigger NETosis pathways.

References

1. Gasdermin D promotes influenza virus-induced mortality through neutrophil amplification of inflammation. Nature Communications (2024).
2. Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection. Nature Communications (2019).
3. Respiratory Syncytial Virus induces the classical ROS-dependent NETosis through PAD-4 and necroptosis pathways activation. Scientific Reports (2018).
4. Neutrophils drive pulmonary vascular leakage in MHV-1 infection of susceptible A/J mice. Frontiers in Immunology (2023).
5. Targeting neutrophils extracellular traps (NETs) reduces multiple organ injury in a COVID-19 mouse model. Respiratory Research (2023).
6. Deficient neutrophil responses early in influenza infection promote viral replication and pulmonary inflammation. PLOS Pathogens (2025).