Cytokine-driven PANoptosis of alveolar macrophages mediated by STAT1 underlies acute lung injury in hypervirulent Klebsiella pneumoniae infection - PubMed
5 hours ago
- #STAT1
- #PANoptosis
- #Klebsiella pneumoniae
- Hypervirulent Klebsiella pneumoniae (hvKp) infection causes significant depletion of alveolar macrophages (AMs) in mice.
- Single-cell RNA sequencing (scRNA-Seq) indicates that AM loss is linked to activation of cell death pathways, specifically PANoptosis (pyroptosis, apoptosis, and necroptosis).
- Pro-inflammatory signaling pathways, including TNF and IFN-II, are significantly enhanced in infected lungs.
- Cytokines, particularly IFN-γ, synergistically induce PANoptosis in macrophages during hvKp infection.
- The transcription factor STAT1 is crucial for PANoptosis activation; STAT1-deficient mice show reduced AM loss, bacterial burdens, and mortality.
- STAT1 deficiency impairs IFN-γ production in immune cells like NK cells, indirectly regulating inflammatory death in AMs.
- The study provides new insights into the pathogenesis of severe Kp infections, highlighting STAT1 and specific cytokines as potential therapeutic targets.