Trichinella spiralis Excretory-Secretory Products Stimulate Host Regulatory T Cell Differentiation through Activating Dendritic Cells

Cells. 2019 Nov 7;8(11):1404. doi: 10.3390/cells8111404.

Abstract

Trichinella spiralis maintains chronic infections within its host, involving a variety of immunomodulatory properties, the mechanisms of which have not been completely elucidated. In this study, we found that T. spiralis infection induced strong regulatory T cell responses through parasite excretory-secretory (ES) products, characterized by increase of CD4+CD25+Foxp3+ and CD4+CD25-Foxp3+ Treg cells accompanied by high levels of IL-10 and TGF-β. T. spiralis adult worm excretory-secretory products (AES) and muscle larvae excretory-secretory products (MES) were both able to activate BMDCs in vitro to facilitate their maturation and to create regulatory cytokines IL-10 and TGF-β. The T. spiralis AES- and MES-pulsed dendritic cells (DCs) possessed abilities not only to present antigens to sensitized CD4+ T cell to stimulate their proliferation but also to induce naive CD4+ T cells to differentiate to Treg cells secreting IL-10 and TGF-β. The passive transfer of T. spiralis AES- and MES-pulsed bone marrow-derived dendritic cells (BMDCs) conferred the naive mice to acquire the differentiation of Treg cells. T. spiralis AES possesses a better ability to induce Treg cells than did MES, although the latter has the ability to induce CD4+CD25-Foxp3+ Treg cells. The results obtained in this study suggested that T. spiralis ES products stimulate the differentiation of host Treg cells possibly through activating dendritic cells to create a regulatory environment that benefits the survival of the parasite in the host.

Keywords: CD4+ T cell; Trichinella spiralis; dendritic cells; excretory–secretory products; regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Helminth / immunology*
  • Biomarkers
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Female
  • Forkhead Transcription Factors / metabolism
  • Gene Expression
  • Gene Expression Profiling
  • Helminth Proteins / immunology*
  • Host-Parasite Interactions / immunology*
  • Lymphocyte Activation / immunology*
  • Mice
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Transcriptome
  • Trichinella spiralis / immunology*
  • Trichinella spiralis / metabolism

Substances

  • Antigens, Helminth
  • Biomarkers
  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Helminth Proteins
  • excretory-secretory antigen, Trichinella