Excretory/secretory products of Angiostrongylus cantonensis fifth-stage larvae induce endoplasmic reticulum stress via the Sonic hedgehog pathway in mouse astrocytes

Background Angiostrongylus cantonensisis an important food-borne zoonotic parasite. Humans are non-permissive hosts, and this parasite develops into fifth-stage larvae (L5) in the brain and subarachnoid cavity and then induces eosinophilic meningitis and eosinophilic meningoencephalitis. Excretory/secretory products (ESPs) are valuable targets for the investigation of host-parasite interactions. These products contain a wide range of molecules for penetrating defensive barriers and avoiding the immune response of the host. Endoplasmic reticulum (ER) stress has been found to be associated with a wide range of parasitic infections and inflammation. ER stress can increase cell survivalviathe activation of downstream signalling. However, the mechanisms of ER stress inA. cantonensisinfection have not yet been clarified. This study was designed to investigate the molecular mechanisms of ER stress in astrocytes after treatment with the ESPs ofA. cantonensisL5. Results The results demonstrated thatA. cantonensisinfection activated astrocytes in the mouse hippocampus and induced the expression of ER stress-related molecules. Next, the data showed that the expression of ER stress-related molecules and the Ca(2+)concentration were significantly increased in activated astrocytes after treatment with the ESPs of L5 ofA. cantonensis. Ultimately, we found that ESPs induced GRP78 expressionviathe Sonic hedgehog (Shh) signalling pathway. Conclusions These findings suggest that in astrocytes, the ESPs ofA. cantonensisL5 induce ER stress and that the Shh signalling pathway plays an important role in this process.