The excretory/secretory products of fifth-stage larval Angiostrongylus cantonensis induces autophagy via the Sonic hedgehog pathway in mouse brain astrocytes

Abstract

Angiostrongyliasis is induced by the nematode Angiostrongylus cantonensis and leads to eosinophilic meningitis and meningoencephalitis in humans. Excretory-secretory products (ESPs) are important investigation targets for studying the relationship between hosts and nematodes. These products assist worms in penetrating the blood-brain barrier and avoiding the host immune response. Autophagy is a catabolic process that is responsible for digesting cytoplasmic organelles, proteins, and lipids and removing them through lysosomes. This process is essential to cell survival and homeostasis during nutritional deficiency, cell injury and stress. In this study, we investigated autophagy induction upon treatment with the ESPs of the fifth-stage larvae (L5) of A. cantonensis and observed the relationship between autophagy and the Shh pathway. First, the results showed that A. cantonensis infection induced blood-brain barrier dysfunction and pathological changes in the brain. Moreover, A. cantonensis L5 ESPs stimulated autophagosome formation and the expression of autophagy molecules, such as LC3B, Beclin, and p62. The data showed that upon ESPs treatment, rapamycin elevated cell viability through the activation of the autophagy mechanism in astrocytes. Finally, we found that ESPs induced the activation of the Sonic hedgehog (Shh) signaling pathway and that the expression of autophagy molecules was increased through the Shh signaling pathway. Collectively, these results suggest that A. cantonensis L5 ESPs stimulate autophagy through the Shh signaling pathway and that autophagy has a protective effect in astrocytes.

Mechanisms of the host immune response and helminth-induced pathology during Trichobilharzia regenti (Schistosomatidae) neuroinvasion in mice

“…Finally, we suggest that the M2 polarization promotes repair of the injured nervous tissue. Astrocyte-mediated IL-6-driven formation of the glial scar, which we observed 14-21 dpi, is commonly considered the primary mechanism of the nervous tissue repair, also known from other helminth neuroinfections [22,98,99]. However, M2 microglia/macrophages promote tissue regeneration and remyelination by driving differentiation of oligodendrocytes [100,101].…”

Effects of Trichinella spiralis and its excretory/secretory products on autophagy of host muscle cells in vivo and in vitro

“…Previous studies have shown that Angiostrongylus cantonensis ES could reduce cell survival. Also, the use of autophagy activator has been shown to enhance cell viability through the activation of the autophagy mechanism in astrocytes [ 15 ]. Given that ES of T .…”

“…Host cell autophagy induced by Toxoplasma gondii and Plasmodium is exploited by the parasites to acquire nutrients, which contributes to their growth and development [ 13 , 14 ]. Recent studies have also revealed that the inhibition of autophagy or excess autophagy can induce cell apoptosis in Echinococcus granulosus [ 15 ].…”

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.…”