Suppression of Sepsis Cytokine Storm by Escherichia Coli Cell Wall-Derived Carbon Dots

Abstract

Sepsis is a life-threatening disease caused by a dysregulated immune response to infection, often involving the translocation of Gram-negative bacteria such as Escherichia coli (E. coli) into the bloodstream, triggering a cytokine storm. Despite its severity, no effective drugs currently exist for sepsis treatment. This study explores whether pathogen-derived carbon dots can mitigate their inherent toxicity while leveraging their structural similarity to pathogens to competitively bind pattern recognition receptors, thereby inhibiting sepsis. Based on this concept, E. coli wall-derived carbon dots (E-CDs) are synthesized and shown to reduce inflammatory cytokine production, protect organ function, and improve survival in septic mice. Mechanistic studies reveal that E-CDs competitively bind to lipopolysaccharide-binding protein with lipopolysaccharide, promoting toll-like receptor 4 degradation via the lysosomal pathway and inhibiting nuclear factor kappa-B (NF-κB) activation. Additionally, E-CDs exhibit antioxidant properties, reducing oxidative stress and mitochondrial DNA release, thereby suppressing overactivation of the stimulator of interferon genes pathway. In septic cynomolgus monkeys and patient-derived peripheral blood mononuclear cells, E-CDs alleviate inflammation and oxidative stress. Overall, this study demonstrates that E-CDs can suppress the cytokine storm in sepsis by co-silencing innate immune pathways, suggesting that converting pathogens into carbon dots offers a novel therapeutic strategy.