Neutrophil Extracellular Traps in Viral Infections: Regulation, Immune Consequences, and Pathogenic Outcomes

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Neutrophils are crucial innate immune cells involved in host defense against viruses.
• Neutrophil extracellular traps (NETs), web-like DNA structures, are released by neutrophils to trap pathogens.
• While NETs aid in antiviral immunity, dysregulated formation can lead to immunopathology and tissue damage in viral infections.

Purpose of the Study:

• To provide a comprehensive overview of NET formation and clearance mechanisms in viral infections.
• To explore how viruses modulate NET processes and influence disease outcomes.
• To discuss therapeutic strategies targeting NET formation and clearance.

Main Methods:

• Review of molecular mechanisms of NET formation and clearance.
• Analysis of viral modulation of NETs using SARS-CoV-2 and HBV models.
• Examination of signaling pathways (SYK, MAPKs, NF-κB) in NETosis.
• Exploration of the role of neutrophil heterogeneity and impaired NET clearance.

Main Results:

• NET formation is a double-edged sword in viral infections, contributing to both defense and pathology.
• Viruses can trigger, exploit, or evade NETs, leading to hyperinflammation and tissue injury.
• Impaired NET clearance and low-density neutrophils (LDNs) are linked to chronic inflammation and post-viral syndromes like long COVID.

Conclusions:

• Understanding NET regulation is critical for developing therapies against virus-induced immunopathology.
• Targeting NET formation or clearance offers potential therapeutic strategies for viral diseases.
• NETs play a complex role in viral infections, necessitating context-specific therapeutic approaches.