Regulatory effects of Echinococcus multilocularis extracellular vesicles on RAW264.7 macrophages

Zheng, Yadong; Guo, Xiaola; Su, Meng; Guo, Aijiang; Ding, Juntao; Yang, Jing; Xiang, Haitao; Cao, Xiaoan; Zhang, Shaohua; Ayaz, Murat; Luo, Xuenong

doi:10.1016/j.vetpar.2017.01.012

Cited by 47 publications

(39 citation statements)

References 43 publications

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“…For example, it was shown that EVs released by the gastrointestinal nematode Heligmosomoides polygyrus reduced Th2-type innate immune responses and eosinophilia induced by the allergenic fungus Alternaria, indicating that EVs can modulate the host innate immune response during parasitic infection (7). EVs released by Echinococcus metacestodes interfered with the antigen presentation pathway in murine dendritic cells and regulated macrophage activation through the LPS/TLR4 signaling pathway (8,9). Using animal models of inflammatory diseases, studies have shown that EVs from Nippostrongylus brasiliensis and Fasciola hepatica can protect against inflammatory bowel disease (IBD) by regulating host immune balance (10,11).…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles Derived From Trichinella spiralis Muscle Larvae Ameliorate TNBS-Induced Colitis in Mice

et al. 2020

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Helminths are masters at modulating the host immune response through a wide variety of versatile mechanisms. These complex strategies facilitate parasite survival in the host and can also be exploited to prevent chronic immune disorders by minimizing excessive inflammation. Extracellular vesicles (EVs) are small membrane-bound structures secreted by helminths which mediate immune evasion during parasite infection. The goal of this study was to investigate the immunoregulatory properties of Trichinella spiralis EVs (Ts-EVs) in a murine model of colitis. We found that Ts-EVs significantly ameliorated 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Ts-EVs alleviated intestinal epithelium barrier damage, markedly reduced pro-inflammatory cytokine secretion and neutrophil infiltration, and upregulated immunoregulatory cytokine expression in colon tissue. Ts-EVs also modulated the adaptive immune response by influencing T-cell composition. The numbers of Th1 and Th17 cells in MLNs, as well as the expression levels of Th1/Th17-associated cytokines and transcription factors in colon were reduced. In contrast, Th2 and Treg cells were increased after Ts-EVs treatment. Furthermore, sequencing of EV-derived microRNAs (miRNAs) indicated that an array of miRNAs was involved in the regulation of the host immune response, including inflammation. These findings expand our knowledge of host-parasite interactions, and may help design novel and effective strategies to prevent parasite infections or to treat inflammatory diseases like IBD. Further studies are needed to identify the specific cargo molecules carried by Ts-EVs and to clarify their roles during T. spiralis infection.

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Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles Derived From Trichinella spiralis Muscle Larvae Ameliorate TNBS-Induced Colitis in Mice

et al. 2020

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“…The nematode's miRNAs were shown to downregulate host Il33r and Dusp1 in vitro, leading to the suppression of the Th2 innate immune response to an allergen in vivo (Buck et al, 2014). This pioneer work was followed by several further reports on other helminths (Wang et al, 2015a;Zamanian et al, 2015;Fromm et al, 2017;Zheng et al, 2017;Eichenberger et al, 2018a,c;non-exhaustive list).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicle-Contained microRNA of C. elegans as a Tool to Decipher the Molecular Basis of Nematode Parasitism

Duguet

Soichot

Kuzyakiv

et al. 2020

Front. Cell. Infect. Microbiol.

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Among the fundamental biological processes affected by microRNAs, small regulators of gene expression, a potential role in host-parasite communication is intriguing. We compared the miRNA complement of extracellular vesicles released by the free-living nematode Caenorhabditis elegans in culture to that of other adult parasitic nematodes. Expecting convergent functional roles for secreted miRNAs due to the common parasitic lifestyle of the organisms under investigation, we performed a miRNA sequence analysis as well as target search and pathway enrichment for potential mRNA targets within host immune functions. We found that the parasite miRNA seed sequences were more often identical to those of C. elegans, rather than to those of their hosts. However, we observed that the nematode-secreted miRNA fractions shared more often seed sequences with host miRNAs than those that are not found in the extracellular environment. Development and proliferation of immune cells was predicted to be affected several-fold by nematode miRNA release. In addition, we identified the AGE-RAGE signaling as a convergent targeted pathway by species-specific miRNAs from several parasitic species. We propose a multi-species comparative approach to differentiate those miRNAs that may have critical functions in host modulation, from those that may not. With our simple analysis, we put forward a workflow to study traits of parasitism at the miRNA level. This work will find even more resonance and significance, as an increasing amount of parasite miRNA collections are expected to be produced in the future.

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“…We show herein that N. caninum EVs are spherical vesicles with 50–150 nm in diameter, the same characteristics as classical exosome-like EVs ( 36 ). Proteomics results showed that N. caninum EVs were enriched in secreted and membrane-associated proteins, including the 14-3-3 and HSP70 and HSP90, which have been extensively used for exosome definition in E. multilocularis ( 37 ) and Leishmania ( 29 ). Studies have shown that EVs could use direct membrane fusion or receptor-mediated mechanism to transfer genetic materials, proteins, and lipids to cells ( 14 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Secreted by Neospora caninum Are Recognized by Toll-Like Receptor 2 and Modulate Host Cell Innate Immunity Through the MAPK Signaling Pathway

Gong

Tai

et al. 2018

Front. Immunol.

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Neospora caninum is an obligate intracellular parasite, which causes significant economic losses in the cattle industry. However, the immune mechanism of the parasite–host interaction is not yet fully understood. Extracellular vesicles (EVs) have emerged as a ubiquitous mechanism by which almost all cells, especially immune and tumor cells, participate in intercellular communications. Although studies have indicated that EVs secreted by Toxoplasma gondii or Trypanosoma brucei promote exchanges of biological molecules important for the host–parasite interplay, however, EVs and their biological activities in N. caninum is not clear. Here, we used multiple methods, including electron microscopy, nanoparticle tracking analysis, RT-PCR, immunofluorescence, western blot, proteomics, and cytokine analyses, to examine the properties of N. caninum EVs. We found that N. caninum produced EVs that are similar to mammalian exosomes, which generally range from 30 to 150 nm in diameter. It was shown that N. caninum EVs could remarkably increase the production of pro-inflammatory cytokines IL-12p40, TNF-α, IL-1β, IL-6, and IFN-γ by wild-type (WT) mouse bone marrow-derived macrophages (BMDMs) whereas the secretion of IL-12p40, TNF-α, and IFN-γ was very strongly downregulated in TLR2−/− mouse BMDMs. The levels of IL-6 were not affected, but the secretion of IL-10 was upregulated. We found that the phosphorylation levels of P38, ERK, and JNK were significantly reduced in the TLR2−/− cells compared with those in WT mouse BMDMs and that treatment with chemical inhibiters of P38, ERK, and JNK resulted in upregulation of IL-6, IL-12p40, and IL-10 production. Together, these results demonstrated that N. caninum EVs could be rapidly internalized to deliver proteins to the host cells and modulate the host cell immune responses through MAPK signaling pathway in a TLR2-dependent manner. Our study is the first to reveal potential roles for N. caninum EVs in host communication and immune response in parasite–host interactions.

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Regulatory effects of Echinococcus multilocularis extracellular vesicles on RAW264.7 macrophages

Cited by 47 publications

References 43 publications

Extracellular Vesicles Derived From Trichinella spiralis Muscle Larvae Ameliorate TNBS-Induced Colitis in Mice

Extracellular Vesicles Derived From Trichinella spiralis Muscle Larvae Ameliorate TNBS-Induced Colitis in Mice

Extracellular Vesicle-Contained microRNA of C. elegans as a Tool to Decipher the Molecular Basis of Nematode Parasitism

Extracellular Vesicles Secreted by Neospora caninum Are Recognized by Toll-Like Receptor 2 and Modulate Host Cell Innate Immunity Through the MAPK Signaling Pathway

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