Echinococcus multilocularis Calreticulin Interferes with C1q-Mediated Complement Activation

Xian, Siqi; Chen, Lujuan; Yan, Yan; Chen, Jianfang; Yu, Guixia; Shao, Yuxiao; Zhan, Bin; Wang, Yanhai; Zhao, Limei

doi:10.3390/tropicalmed8010047

Cited by 3 publications

(2 citation statements)

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“…It has been shown that CRTs are highly conserved in several parasite species, from protozoa ( Trypanosoma , Amoeba , and Leishmania ) to helminths ( Echinococcus , Opisthorchis viverrini , Brugia malayi and Necator americanus ), and play important roles in the adaptation of parasites to the hostile environments and escape from host immune responses ( 4 , 7 , 21 , 45 , 46 ). Our previous studies have determined that TsCRT can bind to human complement C1q and inhibit C1q-initiated classical complement activation to enable the parasite to evade host first-line immune attack ( 15 , 16 ).…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of Trichinella spiralis calreticulin and the structural basis of its complement evasion mechanism involving C1q

Jia,

Yu,

et al. 2024

Front. Immunol.

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Helminths produce calreticulin (CRT) to immunomodulate the host immune system as a survival strategy. However, the structure of helminth-derived CRT and the structural basis of the immune evasion process remains unclarified. Previous study found that the tissue-dwelling helminth Trichinella spiralis produces calreticulin (TsCRT), which binds C1q to inhibit activation of the complement classical pathway. Here, we used x-ray crystallography to resolve the structure of truncated TsCRT (TsCRTΔ), the first structure of helminth-derived CRT. TsCRTΔ was observed to share the same binding region on C1q with IgG based on the structure and molecular docking, which explains the inhibitory effect of TsCRT on C1q-IgG–initiated classical complement activation. Based on the key residues in TsCRTΔ involved in the binding activity to C1q, a 24 amino acid peptide called PTsCRT was constructed that displayed strong C1q-binding activity and inhibited C1q-IgG–initiated classical complement activation. This study is the first to elucidate the structural basis of the role of TsCRT in immune evasion, providing an approach to develop helminth-derived bifunctional peptides as vaccine target to prevent parasite infections or as a therapeutic agent to treat complement-related autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%

Crystal structure of Trichinella spiralis calreticulin and the structural basis of its complement evasion mechanism involving C1q

Jia,

Yu,

et al. 2024

Front. Immunol.

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“…These findings suggest that E. multilocularis uses Em CRT to interfere with the host immune attack process, which may be a strategy of immune evasion. This study further indicates that Em CRT could be developed as a vaccine candidate against E. multilocularis infection [ 5 ]. The third study aimed to investigate the maternal-fetal immune transfer of Nipah virus [ 6 ].…”

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confidence: 81%

Advancement in Understanding Immune Responses against Zoonotic Infections

Tang

Jiang

2023

TropicalMed

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Regulation of immune response against third-stage Gnathostoma spinigerum larvae by human genes

Puasri,

Dechkhajorn,

Dekumyoy

et al. 2023

Front. Immunol.

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BackgroundGnathostomiasis is an important zoonosis in tropical areas that is mainly caused by third-stage Gnathostoma spinigerum larvae (G. spinigerum L3).ObjectivesThis study aimed to prove whether G. spinigerum L3 produces extracellular vesicles (EVs) and investigate human gene profiles related to the immune response against the larvae.MethodsWe created an immune cell model using normal human peripheral blood mononuclear cells (PBMCs) co-cultured with the larvae for 1 and 3 days, respectively. The PBMCs were harvested for transcriptome sequencing analysis. The EV ultrastructure was examined in the larvae and the cultured medium.ResultsExtracellular vesicle-like particles were observed under the larval teguments and in the pellets in the medium. RNA-seq analysis revealed that 2,847 and 3,118 genes were significantly expressed on days 1 and 3 after culture, respectively. The downregulated genes on day 1 after culture were involved in pro-inflammatory cytokines, the complement system and apoptosis, whereas those on day 3 were involved in T cell-dependent B cell activation and wound healing. Significantly upregulated genes related to cell proliferation, activation and development, as well as cytotoxicity, were observed on day 1, and genes regulating T cell maturation, granulocyte function, nuclear factor-κB and toll-like receptor pathways were predominantly observed on day 3 after culture.ConclusionG. spinigerum L3 produces EV-like particles and releases them into the excretory-secretory products. Overall, genotypic findings during our 3-day observation revealed that most significant gene expressions were related to T and B cell signalling, driving T helper 2 cells related to chronic infection, immune evasion of the larvae, and the pathogenesis of gnathostomiasis. Further in-depth studies are necessary to clarify gene functions in the pathogenesis and immune evasion mechanisms of the infective larvae.

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Echinococcus multilocularis Calreticulin Interferes with C1q-Mediated Complement Activation

Cited by 3 publications

References 37 publications

Crystal structure of Trichinella spiralis calreticulin and the structural basis of its complement evasion mechanism involving C1q

Crystal structure of Trichinella spiralis calreticulin and the structural basis of its complement evasion mechanism involving C1q

Advancement in Understanding Immune Responses against Zoonotic Infections

Regulation of immune response against third-stage Gnathostoma spinigerum larvae by human genes

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