calcium-binding protein Cs16 causes acute hepatic injury possibly by reprogramming the metabolic pathway of bone marrow-derived monocytes.

Introduction: infection results in various complications in the liver and biliary systems and is a neglected tropical disease in Eastern Asia. In this study, we report that calcium-binding protein Cs16 activates host immune cells and induces immunopathology in liver.

Methods: Immunohistochemistry was used to detect the localization of Cs16 in adult worms. ELISA was used to detect the serum levels of anti-Cs16 IgG antibody in infected humans and mice. Bile duct injection model was used to figure out the role of Cs16 in vivo. RT-qPCR and ELISA were used to detect the cytokine production from Cs16-treated BMMs . Seahorse assay was used to detect the metabolic pathway of Cs16-treated BMMs in vitro.

Result: Cs16 localizes in the tegument and gut of . Humans and mice with infection exhibited increased levels of anti-Cs16-specific antibody. Using the bile duct injection technique, we found that Cs16 induced obvious inflammation and hepatic necrosis . Cs16 treatment caused the upregulation of inflammatory cytokines in innate immune cells. Moreover, Cs16-treated monocytes relied more on the glycolytic metabolic pathway.

Discussion: Our findings suggest that Cs16 is a potential pathogenic factor derived from adult worm. By reprogramming the metabolic pathway of innate immune cells, Cs16 triggers pro-inflammatory responses in the liver, and therefore, Cs16 is a potential target for the prevention and treatment of clonorchiasis.