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

Abstract 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. E...

Full description

Bibliographic Details
Main Authors: Kuang-Yao Chen, Yi-Ju Chen, Chien-Ju Cheng, Kai-Yuan Jhan, Lian-Chen Wang
Format: Article
Language:English
Published: BMC 2020-06-01
Series:Parasites & Vectors
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13071-020-04189-w
_version_ 1818159487490457600
author Kuang-Yao Chen
Yi-Ju Chen
Chien-Ju Cheng
Kai-Yuan Jhan
Lian-Chen Wang
author_facet Kuang-Yao Chen
Yi-Ju Chen
Chien-Ju Cheng
Kai-Yuan Jhan
Lian-Chen Wang
author_sort Kuang-Yao Chen
collection DOAJ
description Abstract 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 Ca2+ 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.
first_indexed 2024-12-11T15:46:46Z
format Article
id doaj.art-62fad6f167304d41a311a0dad8d7ef55
institution Directory Open Access Journal
issn 1756-3305
language English
last_indexed 2024-12-11T15:46:46Z
publishDate 2020-06-01
publisher BMC
record_format Article
series Parasites & Vectors
spelling doaj.art-62fad6f167304d41a311a0dad8d7ef552022-12-22T00:59:41ZengBMCParasites & Vectors1756-33052020-06-0113111110.1186/s13071-020-04189-wExcretory/secretory products of Angiostrongylus cantonensis fifth-stage larvae induce endoplasmic reticulum stress via the Sonic hedgehog pathway in mouse astrocytesKuang-Yao Chen0Yi-Ju Chen1Chien-Ju Cheng2Kai-Yuan Jhan3Lian-Chen Wang4Department of Parasitology, School of Medicine, China Medical UniversityDepartment of Parasitology, School of Medicine, China Medical UniversityDepartment of Parasitology, College of Medicine, Chang Gung UniversityGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung UniversityDepartment of Parasitology, College of Medicine, Chang Gung UniversityAbstract 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 Ca2+ 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.http://link.springer.com/article/10.1186/s13071-020-04189-wAngiostrongylus cantonensisFifth-stage larvaeExcretory/secretory productsAstrocytesEndoplasmic reticulum stressSonic hedgehog pathway
spellingShingle Kuang-Yao Chen
Yi-Ju Chen
Chien-Ju Cheng
Kai-Yuan Jhan
Lian-Chen Wang
Excretory/secretory products of Angiostrongylus cantonensis fifth-stage larvae induce endoplasmic reticulum stress via the Sonic hedgehog pathway in mouse astrocytes
Parasites & Vectors
Angiostrongylus cantonensis
Fifth-stage larvae
Excretory/secretory products
Astrocytes
Endoplasmic reticulum stress
Sonic hedgehog pathway
title Excretory/secretory products of Angiostrongylus cantonensis fifth-stage larvae induce endoplasmic reticulum stress via the Sonic hedgehog pathway in mouse astrocytes
title_full Excretory/secretory products of Angiostrongylus cantonensis fifth-stage larvae induce endoplasmic reticulum stress via the Sonic hedgehog pathway in mouse astrocytes
title_fullStr Excretory/secretory products of Angiostrongylus cantonensis fifth-stage larvae induce endoplasmic reticulum stress via the Sonic hedgehog pathway in mouse astrocytes
title_full_unstemmed Excretory/secretory products of Angiostrongylus cantonensis fifth-stage larvae induce endoplasmic reticulum stress via the Sonic hedgehog pathway in mouse astrocytes
title_short Excretory/secretory products of Angiostrongylus cantonensis fifth-stage larvae induce endoplasmic reticulum stress via the Sonic hedgehog pathway in mouse astrocytes
title_sort excretory secretory products of angiostrongylus cantonensis fifth stage larvae induce endoplasmic reticulum stress via the sonic hedgehog pathway in mouse astrocytes
topic Angiostrongylus cantonensis
Fifth-stage larvae
Excretory/secretory products
Astrocytes
Endoplasmic reticulum stress
Sonic hedgehog pathway
url http://link.springer.com/article/10.1186/s13071-020-04189-w
work_keys_str_mv AT kuangyaochen excretorysecretoryproductsofangiostrongyluscantonensisfifthstagelarvaeinduceendoplasmicreticulumstressviathesonichedgehogpathwayinmouseastrocytes
AT yijuchen excretorysecretoryproductsofangiostrongyluscantonensisfifthstagelarvaeinduceendoplasmicreticulumstressviathesonichedgehogpathwayinmouseastrocytes
AT chienjucheng excretorysecretoryproductsofangiostrongyluscantonensisfifthstagelarvaeinduceendoplasmicreticulumstressviathesonichedgehogpathwayinmouseastrocytes
AT kaiyuanjhan excretorysecretoryproductsofangiostrongyluscantonensisfifthstagelarvaeinduceendoplasmicreticulumstressviathesonichedgehogpathwayinmouseastrocytes
AT lianchenwang excretorysecretoryproductsofangiostrongyluscantonensisfifthstagelarvaeinduceendoplasmicreticulumstressviathesonichedgehogpathwayinmouseastrocytes