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Mouse Trophoblasts Can Provide Antiviral Protection to Embryonic Stem Cells
Author(s) -
Fendereski Mona,
Neupane Biswas,
Bai Fengwei,
Guo YanLin
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.04634
Subject(s) - blastocyst , embryonic stem cell , inner cell mass , biology , trophoblast , immunology , innate immune system , stem cell , immune system , microbiology and biotechnology , virology , placenta , embryo , fetus , embryogenesis , genetics , gene , pregnancy
The blastocyst is the preimplantation embryo that consists of two major components: the inner cell mass (ICM) and the trophectoderm, which give rise to the fetus and placenta, respectively. We have previously reported that embryonic stem cells (ESCs), the major component of the ICM of blastocyst, do not express type I interferons (IFNs) and lack response to inflammatory cytokines. One would assume that this could make ESCs susceptible to infection. Surprisingly ESCs are less susceptible to immunological cytotoxicity and are not hypersensitive to viral infection. These findings led to our hypothesis that the lack of antiviral responses could be a protective mechanism that allows ESCs to avoid negative impact of immune responses, but how ESCs deal with pathogen infection and immunological challenges is not known. In this study, we investigated IFN‐based antiviral innate immunity of the trophectoderm by using mouse trophoblast stem cells (TSCs) and their in vitro differentiated trophoblasts (TSC‐TBs). Unlike ESCs, our data indicated that both TSCs and TSC‐TBs have a functional IFN system as indicated by their ability to express IFNα, IFNβ, and IFNλ in respond to viral stimuli. They express IFN‐stimulated genes when treated with IFNα and IFNβ. We further showed that the conditioned medium from TSCs and TSC‐FBs stimulated with polyinosinic:polycytidylic acid (poly I:C), a synthetic viral RNA analog, contains antiviral activity that could inhibit infection of ESCs by Chikungunya and Zika virus, similar to the effect of purified IFNβ. These findings indicate that embryonic cell lineages in the blastocyst have different immunological properties at the same developmental stage. Although ESCs are deficient in producing IFNs, they can gain IFN antiviral protection from the trophectoderm via a paracrine signaling mechanism in the blastocyst. Therefore, lacking the production of IFN in ESCs could be a protective mechanism that allows ESCs to avoid the potential harmful impact of immune responses without compromising their antiviral innate immunity. Support or Funding Information This work was in part supported by the National Institute of General Medical Sciences (R15GM128196‐01). We thank Mississippi‐IDeA Network of Biomedical Research Excellence for the use of the imaging facility (funded by the National Institute of General Medical Sciences P20 GM103476‐11).