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

• Published in: Parasites & vectors 2020-06, Vol.13 (1), p.317-317, Article 317
• Main Authors: Chen, Kuang-Yao, Chen, Yi-Ju, Cheng, Chien-Ju, Jhan, Kai-Yuan, Wang, Lian-Chen
• Format: Article
• Language: English
• Subjects: Angiostrongylus cantonensis; Angiostrongylus cantonensis - growth & development; Angiostrongylus cantonensis - metabolism; Angiostrongylus cantonensis - pathogenicity; Animals; Antibodies; Apoptosis; Astrocytes; Astrocytes - metabolism; Astrocytes - pathology; Autophagy; Brain; Brain - metabolism; Brain - parasitology; Brain - pathology; Calcium; Calcium - metabolism; Calcium ions; Cell activation; Cell survival; Defence mechanisms; Endoplasmic reticulum; Endoplasmic reticulum stress; Endoplasmic Reticulum Stress - genetics; Excretory/secretory products; Fifth-stage larvae; Gene expression; Health aspects; Heat-Shock Proteins - metabolism; Hedgehog protein; Hedgehog Proteins - metabolism; Host-Parasite Interactions; Immune response; Immunity; Infections; Inflammation; Laboratory animals; Larva - growth & development; Larva - metabolism; Larva - pathogenicity; Larvae; Leukocytes (eosinophilic); Meningitis; Meningoencephalitis; Mice; Mice, Inbred BALB C; Molecular modelling; Oxidative stress; Parasites; Parasitic diseases; Protein expression; Proteins; Rats; Rats, Sprague-Dawley; Secretory products; Signal Transduction; Signaling; Software; Sonic hedgehog pathway; Stress; Strongylida Infections - parasitology; Strongylida Infections - pathology; Survival; Transcription factors; Zoonoses
• ISSN: 1756-3305; 1756-3305
• DOI: 10.1186/s13071-020-04189-w

Angiostrongylus cantonensis is 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 survival via the activation of downstream signalling. However, the mechanisms of ER stress in A. cantonensis infection have not yet been clarified. This study was designed to investigate the molecular mechanisms of ER stress in astrocytes after treatment with the ESPs of A. cantonensis L5. The results demonstrated that A. cantonensis infection 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 concentration were significantly increased in activated astrocytes after treatment with the ESPs of L5 of A. cantonensis. Ultimately, we found that ESPs induced GRP78 expression via the Sonic hedgehog (Shh) signalling pathway. These findings suggest that in astrocytes, the ESPs of A. cantonensis L5 induce ER stress and that the Shh signalling pathway plays an important role in this process.