Molecular iron-oxo clusters ameliorate sepsis via enhancing humoral immune response

Abstract

Metal-based antimicrobial materials have been extensively studied and applied over decades. While these materials are notably characterized by their superior antibacterial performance and low propensity to induce drug resistance, critical limitations such as inherent cytotoxicity, poor solubility, and instability in aqueous solution remain significant challenges requiring systematic optimization. In this study, we synthesized water-soluble molecular iron-oxo clusters (MIC) with excellent biosafety and stability of aqueous solution. Our findings demonstrate that MIC exhibits marked therapeutic efficacy in cecal ligation and puncture induced sepsis models, a critical validation given sepsis' etiology as a life-threatening infection mediated systemic inflammatory syndrome. MIC combats bacteria by enhancing humoral immune responsiveness. MIC significantly improved the survival rate, reduced bacterial burden, stabilized body temperature, and modulated cytokine profiles in mice with sepsis. Further investigations revealed that MIC promotes B cells proliferation and oxidative phosphorylation, and mitigates mitochondrial damage and apoptosis in B cells, suggesting its role in modulating cellular metabolism. RNA sequencing analysis demonstrated that MIC exerts its effects by influencing key pathways involved in humoral immunity, inflammatory responses, and metabolic adaptation. These findings establish MIC as a novel therapeutic agent for regulating immune responses in sepsis, providing innovative strategies to improve recovery from this life-threatening condition.