Gasdermin D-dependent neutrophil pyroptosis exacerbates Coxsackievirus A6-induced neuroinflammation through NET formation - PubMed
3 hours ago
- #Neutrophil Pyroptosis
- #Neuroinflammation
- #Gasdermin D
- CVA6 infection activates the Caspase-1/GSDMD pathway in neutrophils, leading to pyroptosis and NET release, which exacerbates neuroinflammation and brain injury.
- Genetic knockout (Caspase-1, GSDMD) or pharmacological inhibition (belnacasan, disulfiram) of this pathway reduces NETosis, improves survival, and lessens neuropathology in mice.
- Neutrophil-specific PAD4 knockout improves outcomes, whereas global neutrophil depletion worsens infection, indicating a dual role for neutrophils in defense and pathology.
- Clinical data from HFMD patients show a positive correlation between GSDMD expression and NETosis markers, supporting the translational relevance of the findings.
- The study identifies GSDMD as a promising therapeutic target to mitigate excessive inflammation while preserving essential host defenses during enteroviral infections.