Necroptosis and Caspase-2-Mediated Apoptosis of Astrocytes and Neurons, but Not Microglia, of Rat Hippocampus and Parenchyma Caused by Angiostrongylus cantonensis Infection

Zhou, Hongli; Chen, Zhe; Limpanont, Yanin; Hu, Yue; Ma, Yu-Bin; Huang, Ping; Dekumyoy, Paron; Zhou, Ming; Cheng, Yong; Lv, Ziquan

doi:10.3389/fmicb.2019.03126

Cited by 8 publications

(9 citation statements)

References 94 publications

(83 reference statements)

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“…Furthermore, the interaction between RIP1 and FADD/Caspase-8 was notably enhanced after AC infection. In addition, we performed immunofluorescence to identify astrocytes undergoing apoptosis and this was similar to the outcome of astrocytes in rats infected with AC (Zhou et al 2019 ). For TNF-α-induced necroptosis, previous studies indicated that the downstream signalling axis was the RIP1/RIP3/MLKL pathway characterized by the formation of the RIP1/RIP3/MLKL complex (Wang et al 2019 ; Zhang et al 2018 ).…”

Section: Discussionmentioning

confidence: 91%

“…AC infection remains the main causative agent of eosinophilic meningitis worldwide (Flerlage et al 2017 ). As non-permissive hosts of AC (Ji et al 2017 ; Zhou et al 2019 ), mice and human beings could be infected by eating raw or uncooked snails containing third-stage larvae, which causes severe eosinophilic meningitis or encephalitis (Mengying et al 2017 ). Patients infected by AC suffered from a drastic inflammatory response in the host, neurological impairment and neurodegenerative lesions (Yan et al 2018 ; Yoshida et al 1996 ), finally leading to memory and cognitive deterioration as a result of the impaired function and irreversible cell death of brain cells (Mengying et al 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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TNF-α Triggers RIP1/FADD/Caspase-8-Mediated Apoptosis of Astrocytes and RIP3/MLKL-Mediated Necroptosis of Neurons Induced by Angiostrongylus cantonensis Infection

Zhou

et al. 2021

Cell Mol Neurobiol

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Angiostrongylus cantonensis (AC) can cause severe eosinophilic meningitis or encephalitis in non-permissive hosts accompanied by apoptosis and necroptosis of brain cells. However, the explicit underlying molecular basis of apoptosis and necroptosis upon AC infection has not yet been elucidated. To determine the specific pathways of apoptosis and necroptosis upon AC infection, gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) analysis for gene expression microarray (accession number: GSE159486) of mouse brain infected by AC revealed that TNF-α likely played a central role in the apoptosis and necroptosis in the context of AC infection, which was further confirmed via an in vivo rescue assay after treating with TNF-α inhibitor. The signalling axes involved in apoptosis and necroptosis were investigated via immunoprecipitation and immunoblotting. Immunofluorescence was used to identify the specific cells that underwent apoptosis or necroptosis. The results showed that TNF-α induced apoptosis of astrocytes through the RIP1/FADD/Caspase-8 axis and induced necroptosis of neurons by the RIP3/MLKL signalling pathway. In addition, in vitro assay revealed that TNF-α secretion by microglia increased upon LSA stimulation and caused necroptosis of neurons. The present study provided the first evidence that TNF-α was secreted by microglia stimulated by AC infection, which caused cell death via parallel pathways of astrocyte apoptosis (mediated by the RIP1/FADD/caspase-8 axis) and neuron necroptosis (driven by the RIP3/MLKL complex). Our research comprehensively elucidated the mechanism of cell death after AC infection and provided new insight into targeting TNF-α signalling as a therapeutic strategy for CNS injury.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

TNF-α Triggers RIP1/FADD/Caspase-8-Mediated Apoptosis of Astrocytes and RIP3/MLKL-Mediated Necroptosis of Neurons Induced by Angiostrongylus cantonensis Infection

Zhou

et al. 2021

Cell Mol Neurobiol

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“…Briefly, the cells were fixed in 2.5% glutaraldehyde (GA, Sigma-Aldrich, St. Louis, MO, USA) at 4 °C overnight and dehydrated in ethanol. The samples were captured using a TEM as described previously [ 35 ].…”

Section: Methodsmentioning

confidence: 99%

Downregulation of miR-155-5p enhances the anti-tumor effect of cetuximab on triple-negative breast cancer cells via inducing cell apoptosis and pyroptosis

Song

Wang

et al. 2021

Aging

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Cetuximab resistance is the main obstacle for the treatment of EGFR overexpression cancer, including triple-negative breast cancer (TNBC). MicroRNA (miRNA)-155-5p is upregulated in TNBC cells; thus, the present study explored whether the downregulation of miR-155-5p enhanced the anti-tumor effect of cetuximab in TNBC cells. MDA-MB-231 and MDA-MB-468 cells were infected with lentivirus-epidermal growth factor receptor (EGFR) for 72 h to obtain EGFR-overexpressed cell lines (MDA-MB-231 and MDA-MB-468). The inhibitory effects of cetuximab on the proliferation and migration of EGFR-overexpressed MDA-MB-468 cells were enhanced following transfection with the miR-155-5p antagomir, and miR-155-5p knockdown enhanced the pro-apoptotic effect of cetuximab on EGFR-overexpressed MDA-MB-468 cells. Further, the luciferase reporter assay revealed that gasdermin E (GSDME) was the direct binding target of miR-155-5p. The combination of cetuximab with the miR-155-5p antagomir promoted pyroptosis in EGFR-overexpressed MDA-MB-468 cells via the upregulation of GSDME-N and cleaved caspase-1. Results from the in vivo experiments confirmed that the downregulation of miR-155-5p enhanced the anti-tumor effect of cetuximab in an MDA-MB-468 xenograft model and on EGFR-overexpressed TNBC cells via inducing cell apoptosis and pyroptosis. Therefore, cetuximab combination with an miR-155-5p antagomir may be a novel therapeutic strategy for the treatment of TNBC.

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“…Escamilla et al [ 34 ] confirmed that Fasciola hepatica induced apoptosis in the peritoneal leucocytes of sheep in vivo. Zhou et al [ 35 ] provided the first evidence that neuronal and astrocytic necroptosis and caspase-2-mediated apoptosis are induced by Angiostrongylus cantonensis infection in the parenchymal. In this study, we confirmed that rBsCPI-1 significantly induces cell apoptosis through FCM.…”

Section: Discussionmentioning

confidence: 99%

Regulatory effects of a novel cysteine protease inhibitor in Baylisascaris schroederi migratory larvae on mice immune cells

Xie

et al. 2022

Parasites Vectors

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Background The giant panda (Ailuropoda melanoleuca) is a well-known, rare and endangered species. Baylisascaris schroederi is a pathogenic ascarid. Infection with B. schroederi may cause death in giant pandas. At present, the immune evasion mechanism of B. schroederi is little known. Cysteine protease inhibitors (CPI) play important roles in the regulation of host immune responses against certain nematodes. In this study, we focused on the analysis of the regulation of B. schroederi migratory larvae CPI (rBsCPI-1) on mice immune cells. Methods First, the pattern recognition receptors on the surface of peripheral blood mononuclear cells (PBMCs) and the signal pathways that transduce extracellular signals into the nucleus activated by rBsCPI-1 were identified. Then, the regulatory effects of rBsCPI-1 on PBMCs physiological activities were detected. Finally, the effects of rBsCPI-1 on TLR signaling pathway activation and NF-κB phosphorylation in mice immunized with recombinant protein were analysed. Results The results suggested that rBsCPI-1 secreted by B. schroederi migratory larvae is mainly recognized by TLR2 and TLR4 on PBMCs. Extracellular signals are transduced into the nucleus through the MAPK and NF-κB signaling pathways, enhancing the phagocytosis, migration, and apoptosis of PBMCs; meanwhile, rBsCPI-1 induces high expression of NO. Thus, rBsCPI-1 plays a role in immune regulation. In addition, the high expression of negative regulatory factors also ensured that TLR activation is maintained at the optimal level. Conclusions rBsCPI-1 can transduce regulatory signals into immune cells by activating the TLR2/4-NF-κB/MAPK signaling pathway, having a certain regulatory effect on the physiological activities. Meanwhile, rBsCPI-1 can maintain the immune response in a balance by limiting the over-activation of the TLRs signaling pathway and thus contributes to B. schroederi immune evasion. Graphical Abstract

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Necroptosis and Caspase-2-Mediated Apoptosis of Astrocytes and Neurons, but Not Microglia, of Rat Hippocampus and Parenchyma Caused by Angiostrongylus cantonensis Infection

Cited by 8 publications

References 94 publications

TNF-α Triggers RIP1/FADD/Caspase-8-Mediated Apoptosis of Astrocytes and RIP3/MLKL-Mediated Necroptosis of Neurons Induced by Angiostrongylus cantonensis Infection

TNF-α Triggers RIP1/FADD/Caspase-8-Mediated Apoptosis of Astrocytes and RIP3/MLKL-Mediated Necroptosis of Neurons Induced by Angiostrongylus cantonensis Infection

Downregulation of miR-155-5p enhances the anti-tumor effect of cetuximab on triple-negative breast cancer cells via inducing cell apoptosis and pyroptosis

Regulatory effects of a novel cysteine protease inhibitor in Baylisascaris schroederi migratory larvae on mice immune cells

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