Who and how, DNA sensors in NETs-driven inflammation

Area of Science:

• Immunology
• Molecular Biology
• Inflammation Research

Background:

• Neutrophil extracellular traps (NETs) are crucial for trapping microbes during infection.
• In sterile inflammation, NETs are linked to tissue damage and uncontrolled inflammatory responses.
• DNA released during sterile inflammation acts as both a NETs activator and an immunogenic molecule.

Purpose of the Study:

• To review the role of DNA sensors in NETs formation and detection during sterile inflammation.
• To elucidate the contribution of specific DNA sensors to NETs-driven inflammation.
• To identify knowledge gaps and propose future therapeutic strategies targeting DNA sensors and NETs.

Main Methods:

• Literature review of studies on DNA sensors and NETs in sterile inflammation.
• Analysis of the roles of Toll-like receptor-9 (TLR9), cyclic GMP-AMP synthase (cGAS), Nod-like receptor protein 3 (NLRP3), and Absence in Melanoma-2 (AIM2).
• Synthesis of current understanding regarding DNA sensor involvement in NETs-driven inflammatory processes.

Main Results:

• Several DNA sensors, including TLR9, cGAS, NLRP3, and AIM2, are implicated in NETs formation and detection.
• The precise mechanisms by which these sensors drive NETs-associated inflammation remain incompletely understood.
• The potential redundancy versus unique functions of these DNA sensors in sterile inflammation require further investigation.

Conclusions:

• DNA sensors play a significant role in NETs formation and inflammation during sterile conditions.
• Further research is needed to clarify the distinct roles of individual DNA sensors and their interplay.
• Understanding these pathways could lead to novel therapeutic interventions for inflammatory diseases.