The regulatory mechanism of NLRP3 inflammasome in the "immune paralytic-overactivation" imbalance in sepsis: the latest progress from molecular signaling to clinical translation.

Sepsis remains a major challenge in critical care medicine worldwide, characterized by a dynamic imbalance of the immune system between two extremes: "immunoparalysis" and "hyperactivation." This dysregulation severely affects patient survival. The NLRP3 inflammasome, a central molecular platform in innate immunity, has recently been shown to play a critical dual role in the pathogenesis of sepsis. This review systematically outlines the structural features and activation mechanisms of the NLRP3 inflammasome, elaborates on its pro-inflammatory and immunosuppressive effects in sepsis-induced immune dysregulation, and summarizes the associated signaling pathways and regulatory networks. By integrating recent advances in basic and clinical research, we provide an in-depth analysis of the molecular regulatory mechanisms of the NLRP3 inflammasome in sepsis and evaluate its potential as a therapeutic target. Furthermore, this review discusses the opportunities and challenges in translating NLRP3-targeted strategies into clinical practice, emphasizing the potential of precise NLRP3 modulation to restore immune homeostasis in sepsis. Our findings may provide a theoretical foundation and future research directions for developing novel therapeutic approaches.