Research on the role of Gasdermin D (GSDMD) in influenza A virus (IAV) infection reveals its impact on inflammation and mortality.
Extract
[...] Question 6 The GSDMD bands were analyzed at two distinct heights to differentiate between the full-length GSDMD and the active cleaved form, which is responsible for pore formation. GSDMD is activated in the infected lungs of WT mice. Question 7 High levels of inflammatory cytokines measured by ELISA in the lungs indicate systemic inflammation symptoms in IAV-infected mice. However, inflammation is reduced in Gsdmd-/- mice, which have lower levels of these cytokines, suggesting that GSDMD exacerbates systemic inflammation in response to infection. [...]
[...] Without GSDMD, this release is reduced. Question 9 The decrease in IFN? in Gsdmd-/- mice is due to a reduction in the level of activation of RIG-I, a pathogen recognition receptor (PRR) that detects the viral RNA of IAV. RIG-I stimulates the transcription factors IRF3 and promoting the production of IFN?, a key element of the antiviral response. The activation of this pathway is inhibited in the absence of GSDMD, which restricts the induction of IFN? and decreases the inflammatory response. [...]
[...] Gasdermin D promotes influenza virus-induced mortality through neutrophil amplification of inflammation. Nat Commun (2024). https://doi.org/10.1038/s41467-024-47067-0 Link to the article : https://doi.org/10.1038/s41467-024-47067-0 Question 1 The influenza A virus (IAV) replication cycle is not directly affected by GSDMD, as viral loads in the lungs of infected mice were comparable between wild-type and Gsdmd-/- mice. The suppression of GSDMD did not affect viral multiplication, indicating that GSDMD plays a primary role in the inflammatory response rather than in viral replication. Question 2 A reduction in IFN? [...]
