Abstract

Cystic echinococcosis (CE) is a zoonotic parasitic disease spread worldwide caused by Echinococcus granulosus (Eg), which sometimes causes serious damage; however, in many cases, people are not aware that they are infected. A number of recombinant vaccines based on Eg are used to evaluate their effectiveness against the infection. Our previous report showed that recombinant Eg.P29 (rEg.P29) has a marvelous immunoprotection and can induce Th1 immune response. Furthermore, data of miRNA microarray in mice spleen CD4+ T cells showed that miR-126a-5p was significantly elevated 1 week after immunization by using rEg.P29. Therefore, in this perspective, we discussed the role of miR-126a-5p in the differentiation of naive CD4+ T cells into Th1/Th2 under rEg.P29 immunization and determined the mechanisms associated with delta-like 1 homolog (DLK1) and Notch1 signaling pathway. One week after P29 immunization of mice, we found that miR-126a-5p was significantly increased and DLK1 expression was decreased, while Notch1 pathway activation was enhanced and Th1 response was significantly stronger. The identical conclusion was obtained by overexpression of mmu-miR-126a-5p in primary naive CD4+ T cells in mice. Intriguingly, mmu-miR-126a-5p was significantly raised in serum from mice infected with protoscolex in the early stages of infection and markedly declined in the late stages of infection, while has-miR-126-5p expression was dramatically reduced in serum from CE patients. Taken together, we show that miR-126a-5p functions as a positive regulator of Notch1-mediated differentiation of CD4+ T cells into Th1 through downregulating DLK1 in vivo and in vitro. Hsa-miR-126-5p is potentially a very promising diagnostic biomarker for CE.

Highlights

  • Cystic echinococcosis (CE) is a chronic and neglected complicated zoonotic parasitic disease that is prevalent mainly in areas with developed animal husbandry (1, 2)

  • The results showed that miR-126a5p, miR-378a-5p, and miR-1247-5p may be involved in the differentiation of CD4+ T cells toward Th1 to protect the organism from Echinococcus granulosus (Eg) infection

  • One week after immunization of mice with rEg.P29, the results of flow cytometry showed significantly higher IFN-g expression producing the Th1 subtype and no significant change in IL-4 expression producing the Th2 subtype in splenic CD4+ T cells compared with the FCA and PBS groups (Figures 1B, C), which is consistent with previous descriptions (20)

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Summary

Introduction

Cystic echinococcosis (CE) is a chronic and neglected complicated zoonotic parasitic disease that is prevalent mainly in areas with developed animal husbandry (1, 2). It is important to note that the early stages of CE do not cause any obvious symptoms and can coexist with the host for a long period of time. The conventional means of diagnosing CE, is unable to make an effective detection of infection in its early stages (6, 7). There are different treatment methods such as percutaneous treatment, surgical treatment, medication, observation, and waiting at different stages of CE (8–11), it is essential to find ways to prevent the occurrence of CE and means to detect it at an early stage. The development of vaccine is a feasible method to prevent the prevalence of CE. Several candidate vaccine molecules have been shown to be highly protective against Echinococcus granulosus (Eg) infection in mice and livestock (12–17). REg.P29 showed 94.5% and 96.6% immune protection in sheep and mice, respectively (15, 18)

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