Clonorchis sinensis cyclophilin A immunization protected mice from CLP-induced sepsis

Abstract

Cyclophilin A (CyPA), ubiquitously existing in cytoplasm of all eukaryotes, can be secreted in response to inflammatory stimuli. Extracellular CyPA plays a prominent role in the pathological processes of inflammatory diseases, acting as a proinflammatory mediator, exerting chemotactic effects, promoting apoptosis of endothelial cells and amplifying ROS generation, thus being considered as a potential treatment target of sepsis, a systemic inflammatory response syndrome. Our previous study found that antibodies against cyclophilin A of Clonorchis sinensis (CsCyPA) could neutralize mouse cyclophilin A (MuCyPA). In this study, we explored whether CsCyPA immunization could prevent or ameliorate mice sepsis induced by cecum ligation puncture (CLP). The results showed that CsCyPA immunization could improve the 72 h survival rate of mice after CLP. Moreover, the protective effect presented in a titer-dependent manner. The levels of cytokine IL-1β, IL-6, TNF-α, MCP-1 and AST in serum were remarkably decreased compared to CLP control group mice. Pathological damages of liver, lung and kidney were ameliorated accompanied by less inflammatory cell infiltration. CFU per whole peripheral blood at 12 h and 24 h after CLP surgery was significantly lower than that of CLP control group. In vitro, intracellular ROS generation and cytokine mRNA expression in peritoneal macrophages stimulated by LPS were reduced obviously with anti-CsCyPA antibodies (anti-CsCyPAs) preincubation. All these results demonstrated that CsCyPA immunization protected mice from CLP induced sepsis.

Keywords: Antibody; Clonorchis sinensis; Cyclopholin A (CyPA); Immunization; Sepsis.