Epithelial Atg5 Deficiency Intensifies Caspase-11 Activation, Fueling Extracellular mtDNA Release to Activate cGAS-STING-NLRP3 Axis in Macrophages during Pseudomonas Infection (IMAGE)
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This work illuminates the essential role of epithelial ATG5 in defending against P. aeruginosa. Atg5 deficiency impairs bacterial clearance and aggravates inflammation via inflammasome activation, and pyroptosis. Mechanistically, impaired mitophagy intensifies mitochondrial damage. This, combined with the enhanced activation of GSDMD mediated by the non-canonical caspase-11 inflammasome, amplifies the extracellular release of mtDNA, triggering cGAS-STING-NLRP3 signaling in macrophages and amplifying lung injury.
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Dr. Guoping Li and Dr. Min Wu
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