Upregulated galectin-1 in Angiostrongylus cantonensis L5 reduces body fat and increases oxidative stress tolerance

Sun, Weiwei; Yan, Xiumei; Qiao, Aijun; Zhang, Yuan-Jiao; Yang, Leixiang; Huang, Huicong; Shi, Hengzhen; Yan, Bowen

doi:10.1186/s13071-022-05171-4

Cited by 4 publications

(2 citation statements)

References 57 publications

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“…Scale bar: 100 μm. Relative Oil Red signal is quantified using ImageJ software [ 47 ]. E , F Relative content of select (C14:0, C16:0, C16:1, C18:0, and C18:1) and total fatty acids in N2, RB1515, and HCON_00092800 rescuing worms.…”

Section: Resultsmentioning

confidence: 99%

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Fatty acid- and retinol-binding protein 6 does not control worm fatty acid content in Caenorhabditis elegans but might play a role in Haemonchus contortus parasitism

Wei

Chen

et al. 2023

Parasites Vectors

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Background Nematodes have lost the ability to synthesise necessary lipids de novo and have complementally evolved the capacity to acquire fatty acids and their derivatives from a diet or host animal. Nematode-specific fatty acid- and retinol-binding protein (FAR) family is one approach that facilitates lipid acquisition, representing an Achilles heel and potential target against roundworms of socioeconomic significance. However, little is known about their detailed functional roles in either free-living or parasitic nematodes. Methods A genome-wide identification and curation were performed to screen the FAR family members of Haemonchus contortus. Their transcription patterns in worms were also analysed to identify the targets. Ligand binding assay and molecular docking were conducted to verify the fatty acid binding activities of FAR proteins of interest. RNA interference (RNAi) and heterologous expression (rescuing) experiments were designed to explore the potential roles of the selected FAR protein in nematodes. Localisation of the protein was shown in sections of paraffin-embedded worms after an immunohistochemistry (IHC) assay. Results Here, an orthologue of far-6 in the model organism Caenorhabditis elegans (Ce-far-6) was functionally characterised in a parasitic nematode, H. contortus (Hc-far-6). It is demonstrated that knockdown of Ce-far-6 gene did not affect worm fat content, reproduction, or lifespan, but decreased worm body length at an early life stage of C. elegans. In particular, the Ce-far-6 mutant associated phenotype was completely rescued by Hc-far-6, suggesting a conserved functional role. Surprisingly, there were distinct tissue expression patterns of FAR-6 in the free-living C. elegans and parasitic H. contortus. High transcriptional level of Hc-far-6 and dominant expression of FAR-6 in the intestine of the parasitic stage of H. contortus link this gene/protein to nematode parasitism. Conclusions These findings substantially enhance our understanding of far genes and the associated lipid biology of this important parasitic nematode at a molecular level, and the approaches established are readily applicable to the studies of far genes in a broad range of parasites. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

“…After washing, worms ( n = 20) were observed and imaged under an LSM 780 confocal fluorescence microscopy (Zeiss, Germany). ImageJ software (NIH Image, Bethesda, MD, USA) was used to quantify the signal intensity of Oil red O staining [ 47 ].…”

Section: Methodsmentioning

confidence: 99%

Fatty acid- and retinol-binding protein 6 does not control worm fatty acid content in Caenorhabditis elegans but might play a role in Haemonchus contortus parasitism

Wei

Chen

et al. 2023

Parasites Vectors

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Extracellular vesicles from fifth-stage larval Angiostrongylus cantonensis upregulate cholesterol biosynthesis and suppress NLRP2-associated inflammatory responses in mouse astrocytes

Cheng,

Wang,

Chu

et al. 2024

mSystems

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Angiostrongylus cantonensis is a zoonotic parasite that causes severe symptoms in humans, including eosinophilic meningitis and eosinophilic meningoencephalitis. Extracellular vesicles (EVs) derived from helminthes have been implicated in regulating host survival and immune response. However, the roles of A. cantonensis EVs in modulating parasite pathogenesis and host immune response remain poorly understood. Herein, we characterized EVs derived from A. cantonensis fifth-stage larvae (L5) and adult worms. Ultrastructural features showed that EVs from adult worms are smaller in size compared with those from L5. Proteomic analysis identified stage-specific proteins packaged in L5 and adult worm EVs. To investigate the crosstalk between L5 EVs and host cells, RNA sequencing analysis was conducted to identify the differentially expressed genes (DEGs) and enriched biological pathways in mouse astrocytes treated with L5 EVs. GO and KEGG enrichment analysis demonstrated that the pathways related to “cholesterol biosynthesis” are significantly upregulated in L5 EV-treated astrocytes. Based on the transcriptomic data, we observed a downregulated trend of NOD-like receptors (NLRs) protein 2 (NLRP2), a key regulator of brain inflammation, in mouse astrocytes treated with L5 EVs. To validate this result, we utilized ATP to induce the expression of NLRP2 inflammasome-related genes and proteins, as well as the secretion of downstream cytokines. Notably, ATP-induced overexpression of NLRP2 inflammasome-related molecules was significantly reduced in mouse astrocytes upon L5 EV treatment. Collectively, our data suggest that A. cantonensis L5 EVs enhance cholesterol synthesis and potentially modulate immune response by reducing NLRP2 inflammasome-related signaling in non-permissive host cells. IMPORTANCE Angiostrongylus cantonensis is a significant causative agent of eosinophilic meningitis and eosinophilic meningoencephalitis in humans. Helminth-derived extracellular vesicles (EVs) are known to play a crucial role in parasite pathogenesis and host immunomodulation. However, the protein compositions of A. cantonensis EVs and their roles in parasite pathogenesis and host immune response remain unclear. Our results demonstrate for the first time the distinct protein compositions in A. cantonensis L5 and adult worm EVs. The highly abundant proteins in L5 EVs that have immunomodulatory or pathogenic potential in the host deserve further investigation. Additionally, the uptake of L5 EVs by mouse astrocytes significantly upregulates cholesterol synthesis and suppresses ATP-induced NLRP2 inflammasome-related signaling. This study highlights the immunomodulatory roles of L5 EVs in non-permissive hosts, suggesting their potential as therapeutic targets and vaccine candidates against A. cantonensis .

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Trichinella spiralis galectin binding to toll-like receptor 4 induces intestinal inflammation and mediates larval invasion of gut mucosa

Ma,

Zhang,

Zhang

et al. 2023

Vet Res

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Previous studies showed that Trichinella spiralis galectin (Tsgal) facilitates larval invasion of intestinal epithelium cells (IECs). However, IEC proteins binding with Tsgal were not identified, and the mechanism by which Tsgal promotes larval invasion is not clear. Toll-like receptors (TLRs) are protein receptors responsible for recognition of pathogens. The aim of this study was to investigate whether recombinant Tsgal (rTsgal) binds to TLR-4, activates inflammatory pathway in gut epithelium and mediates T. spiralis invasion. Indirect immunofluorescence (IIF), GST pull-down and co-immunoprecipitation (Co-IP) assays confirmed specific binding between rTsgal and TLR-4 in Caco-2 cells. qPCR and Western blotting showed that binding of rTsgal with TLR-4 up-regulated the TLR-4 transcription and expression in Caco-2 cells, and activated p-NF-κB p65 and p-ERK1/2. Activation of inflammatory pathway TLR-4/MAPK-NF-κB by rTsgal up-regulated pro-inflammatory cytokines (IL-1β and IL-6) and down-regulated anti-inflammatory cytokine TGF-β in Caco-2 cells, and induced intestinal inflammation. TAK-242 (TLR-4 inhibitor) and PDTC (NF-κB inhibitor) significantly inhibited the activation of TLR-4 and MAPK-NF-κB pathway. Moreover, the two inhibitors also inhibited IL-1β and IL-6 expression, and increased TGF-β expression in Caco-2 cells. In T. spiralis infected mice, the two inhibitors also inhibited the activation of TLR-4/MAPK-NF-κB pathway, ameliorated intestinal inflammation, impeded larval invasion of gut mucosa and reduced intestinal adult burdens. The results showed that rTsgal binding to TLR-4 in gut epithelium activated MAPK-NF-κB signaling pathway, induced the expression of TLR-4 and pro-inflammatory cytokines, and mediated larval invasion. Tsgal might be regarded as a candidate molecular target of vaccine against T. spiralis enteral invasive stage.

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Upregulated galectin-1 in Angiostrongylus cantonensis L5 reduces body fat and increases oxidative stress tolerance

Cited by 4 publications

References 57 publications

Fatty acid- and retinol-binding protein 6 does not control worm fatty acid content in Caenorhabditis elegans but might play a role in Haemonchus contortus parasitism

Fatty acid- and retinol-binding protein 6 does not control worm fatty acid content in Caenorhabditis elegans but might play a role in Haemonchus contortus parasitism

Extracellular vesicles from fifth-stage larval Angiostrongylus cantonensis upregulate cholesterol biosynthesis and suppress NLRP2-associated inflammatory responses in mouse astrocytes

Trichinella spiralis galectin binding to toll-like receptor 4 induces intestinal inflammation and mediates larval invasion of gut mucosa

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