The Recombinant E g.P29-Mediated miR-126a-5p Promotes the Differentiation of Mouse Naive CD4+ T Cells via DLK1-Mediated Notch1 Signal Pathway

Front Immunol. 2022 Feb 8:13:773276. doi: 10.3389/fimmu.2022.773276. eCollection 2022.

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.

Keywords: CD4+ T cells; Cystic Echinococcocosis; DLK1; Notch1; Th1; Th2; miR-126a-5p; rEg.P29.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antigens, Helminth / genetics
  • Antigens, Helminth / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / parasitology
  • Calcium-Binding Proteins / metabolism
  • Case-Control Studies
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Echinococcosis / genetics
  • Echinococcosis / immunology*
  • Echinococcosis / parasitology
  • Echinococcus granulosus / genetics
  • Echinococcus granulosus / immunology*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics
  • MicroRNAs / immunology*
  • Middle Aged
  • Receptor, Notch1 / metabolism
  • Signal Transduction / immunology
  • Th1 Cells / immunology
  • Th1 Cells / parasitology
  • Th2 Cells / immunology
  • Th2 Cells / parasitology
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Zoonoses / genetics
  • Zoonoses / immunology*
  • Zoonoses / parasitology

Substances

  • Antigens, Helminth
  • Calcium-Binding Proteins
  • Dlk1 protein, mouse
  • MicroRNAs
  • P-29 antigen
  • Receptor, Notch1
  • Vaccines, Synthetic