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. 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.

Benzaldehyde Attenuates the Fifth Stage Larval Excretory-Secretory Product of <em>Angiostrongylus cantonensis</em>-Induced Injury in Mouse Astrocytes via Regulation of Endoplasmic Reticulum Stress and Oxidative Stress

“…Because of their importance in nematode pathogenesis, ESPs are an important target in the investigation of host-parasite relationships and research in vaccine candidates and therapeutic targets. In previous investigation, we demonstrated that A. cantonensis ESPs can stimulate oxidative stress, autophagy, ER stress, and cell apoptosis in astrocytes [36][37][38]. However, we used proteomic analysis to profile, identify, and characterize the proteins in the A. cantonensis L5 ESPs.…”

Regulatory effects of Trichinella spiralis and a serine protease inhibitor on the endoplasmic reticulum stress response of intestinal epithelial cells

“…In recent years, many studies have shown that ERS plays a key role in the interaction between the pathogenicity of parasitic infection and the host immune response [ 38 , 39 ]. Therefore, we conducted a series of experiments to explore whether Trichinella spiralis ( T. spiralis ) infection also induced ERS in host intestinal epithelial cells.…”

Decoding the Roles of Astrocytes and Hedgehog Signaling in Medulloblastoma

“…Somatic TERT (telomerase) promoter hotspot mutations are also associated with the SHH subgroup [22,23]. Mutation of PTEN (phosphatase and tensin homolog) is found in more than 5% of human Due to increasing evidence of an association between wound healing and the development of tumors, recent studies have investigated the complex functions of astrocytes involved in the support of medulloblastoma growth, as these specialized glial cells are involved in the functional recovery of the central nervous system (CNS) [29,32,33,[48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64]. Astrocytes are specialized and heterogeneous cells that are essential modulators of local blood flow as well as being involved in the maintenance of homeostasis of extracellular fluids, ions, and transmitters [61,62].…”

“…In response to these non-cell-autonomous stimuli, astrocytes can produce a multitude of molecular signals that can, in turn, influence many different neural and non-neural cell types, including cells involved in innate immune responses [75]. In parasite infections, astrocytes secrete the SHH protein which, in turn, induces the production of GRP78, an endoplasmic reticulum (ER) chaperone from the heat shock protein family [32]. Under ER stress, it is believed that the activation of GRP78 may increase cell survival through the unfolded protein response and may also protect cells from ER-stress-induced apoptosis by activating Bcl-2 and inhibiting Bak, Bax, Caspase, and CHOP [32].…”

“…In parasite infections, astrocytes secrete the SHH protein which, in turn, induces the production of GRP78, an endoplasmic reticulum (ER) chaperone from the heat shock protein family [32]. Under ER stress, it is believed that the activation of GRP78 may increase cell survival through the unfolded protein response and may also protect cells from ER-stress-induced apoptosis by activating Bcl-2 and inhibiting Bak, Bax, Caspase, and CHOP [32]. In fact, astrocytes facilitate the formation of medulloblastoma tumoroids by secreting SHH proteins and generating the astrocyte-derived extracellular matrix [41].…”