Innate immunity in an in vitro murine blastocyst model using embryonic and trophoblast stem cells

Hiroaki Aikawa, Miho Tamai, Keisuke Mitamura, Fakhria Itmainati, Glen N. Barber, Yoh ichi Tagawa

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The immune system has two broad components-innate and adaptive immunity. Adaptive immunity becomes established only after the onset of hematopoiesis, whereas the innate immune system may be actively protecting organisms from microbial invasion much earlier in development. Here, we address the question of whether the innate immune system functions in the early-stage embryo, i.e., the blastocyst. The innate immune system was studied by using in vitro blastocyst models, e.g., embryonic stem (ES) and trophoblast stem (TS) cell cultures. The expression of Toll-like receptors (TLR)-2, -3, and -5 could be detected in both ES and TS cells. The expression of interferon (IFN)-β was induced by the addition of polyinosinic:polycytidylic acid [poly(I:C)] in TS cells, but not ES cells, although TLR-3 was expressed at the same level in both cell types. In turn, ES cells responded to IFN-β exposure by expressing IFN-induced anti-viral genes, e.g., RNA-dependent protein kinase and 2', 5'-oligoadenylate synthetase (OAS). Neither a reduction in ES cell proliferation nor cell death in these cultures was observed after IFN-β stimulation. Furthermore, OAS1a expression was induced in ES/TS co-cultures after poly(I:C) stimulation, but was not induced when either cell type was cultured alone. In conclusion, TS cells react to poly(I:C) stimulation by producing IFN-β, which induces IFN-inducible genes in ES cells. This observation suggests that the trophectoderm, the outer layer of the blastocyst, may respond to viral infection, and then induce anti-viral gene expression via IFN-β signaling to the blastocyst inner cell mass.

Original languageEnglish (US)
Pages (from-to)358-365
Number of pages8
JournalJournal of Bioscience and Bioengineering
Volume117
Issue number3
DOIs
StatePublished - Mar 1 2014

Keywords

  • Blastocyst
  • Embryonic stem cell
  • Innate immunity
  • Toll-like receptors
  • Trophoblast stem cell
  • Type-I interferon

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology
  • Bioengineering

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