Journal Article

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

Chen, Yi-Ju, Chen, Kuang-Yao, Cheng, Chien-Ju, Jhan, Kai-Yuan, Wang, Lian-Chen

2020

Overview

Background 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. Results 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 2+ 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. Conclusions 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Angiostrongylus cantonensis / Angiostrongylus cantonensis - growth & development / Angiostrongylus cantonensis - metabolism / Angiostrongylus cantonensis - pathogenicity / Animals / Antibodies / Apoptosis / Astrocytes / Astrocytes - metabolism / Astrocytes - pathology / Autophagy / Biomedical and Life Sciences / Biomedicine / Brain / Brain - metabolism / Brain - parasitology / Brain - pathology / Calcium / Calcium - metabolism / Calcium ions / Cell activation / Cell survival / cell viability / Defence mechanisms / Endoplasmic reticulum / Endoplasmic Reticulum Chaperone BiP / Endoplasmic reticulum stress / Endoplasmic Reticulum Stress - genetics / Entomology / Excretory/secretory products / Fifth-stage larvae / Gene expression / Health aspects / Heat-Shock Proteins - metabolism / Hedgehog protein / Hedgehog Proteins - metabolism / hippocampus / Host-Parasite Interactions / Immune response / Immunity / Infections / Infectious Diseases / 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 / Parasitology / Parastrongylus cantonensis / 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 / Tropical Medicine / Veterinary Medicine/Veterinary Science / Virology / Zoonoses