Mouse Trophoblast Cells Can Provide IFN-Based Antiviral Protection to Embryonic Stem Cells via Paracrine Signaling

Fendereski, Mona; Neupane, Biswas; Nazneen, Farzana; Bai, Fengwei; Guo, Yan‐Lin

doi:10.4049/jimmunol.2100679

Cited by 2 publications

(1 citation statement)

References 52 publications

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“…These results suggest that the absence of a functional IFN response is characteristic of pluripotent cells, as well as gametes. Instead, adult stem cells and trophoblasts do appear to have a functional IFN response [ 23 , 24 ]. Aside from viruses and dsRNA, mouse ESCs are also not capable of activating an innate immune response against viral DNA mimics such as G3-YSD, lipopolysaccharide (LPS, which mimics bacterial infections) or bacteria [ 17 , 25 , 26 ].…”

Section: The Type-i Ifn Response and Early Developmentmentioning

confidence: 99%

Antiviral Defence Mechanisms during Early Mammalian Development

Mueller,

Witteveldt,

Macias

2024

Viruses

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The type-I interferon (IFN) response constitutes the major innate immune pathway against viruses in mammals. Despite its critical importance for antiviral defence, this pathway is inactive during early embryonic development. There seems to be an incompatibility between the IFN response and pluripotency, the ability of embryonic cells to develop into any cell type of an adult organism. Instead, pluripotent cells employ alternative ways to defend against viruses that are typically associated with safeguard mechanisms against transposable elements. The absence of an inducible IFN response in pluripotent cells and the constitutive activation of the alternative antiviral pathways have led to the hypothesis that embryonic cells are highly resistant to viruses. However, some findings challenge this interpretation. We have performed a meta-analysis that suggests that the susceptibility of pluripotent cells to viruses is directly correlated with the presence of receptors or co-receptors for viral adhesion and entry. These results challenge the current view of pluripotent cells as intrinsically resistant to infections and raise the fundamental question of why these cells have sacrificed the major antiviral defence pathway if this renders them susceptible to viruses.

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Section: The Type-i Ifn Response and Early Developmentmentioning

confidence: 99%

Antiviral Defence Mechanisms during Early Mammalian Development

Mueller,

Witteveldt,

Macias

2024

Viruses

View full text Add to dashboard Cite

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Mouse Trophoblast Cells Have Attenuated Responses to TNF-α and IFN-γ and Can Avoid Synergic Cytotoxicity of the Two Cytokines

Fendereski,

Ming,

Jiang

et al. 2023

The Journal of Immunology

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TNF-α and IFN-γ are two inflammatory cytokines that play critical roles in immune responses, but they can also negatively affect cell proliferation and viability. In particular, the combination of the two cytokines (TNF-α/IFN-γ) synergistically causes cytotoxicity in many cell types. We recently reported that mouse embryonic stem cells (ESCs) isolated from the blastocyst stage embryo do not respond to TNF-α and have limited response to IFN-γ, thereby avoiding TNF-α/IFN-γ cytotoxicity. The current study expanded our investigation to mouse trophoblast stem cells (TSCs) and their differentiated trophoblasts (TSC-TBs), the precursors and the differentiated cells of the placenta, respectively. In this study, we report that the combination of TNF-α/IFN-γ does not show the cytotoxicity to TSCs and TSC-TBs that otherwise effectively kills fibroblasts, similar to ESCs. Although ESCs, TSCs, and TSC-TBs are dramatically different in their growth rate, morphology, and physiological functions, they nevertheless share a similarity in being able to avoid TNF-α/IFN-γ cytotoxicity. We propose that this unique immune property may serve as a protective mechanism that limits cytokine cytotoxicity in the blastocyst. With molecular and cellular approaches and genome-wide transcriptomic analysis, we have demonstrated that the attenuated NF-κB and STAT1 transcription activation is a limiting factor that restricts the effect of TNF-α/IFN-γ on TSCs and TSC-TBs.

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Mouse Trophoblast Cells Can Provide IFN-Based Antiviral Protection to Embryonic Stem Cells via Paracrine Signaling

Cited by 2 publications

References 52 publications

Antiviral Defence Mechanisms during Early Mammalian Development

Antiviral Defence Mechanisms during Early Mammalian Development

Mouse Trophoblast Cells Have Attenuated Responses to TNF-α and IFN-γ and Can Avoid Synergic Cytotoxicity of the Two Cytokines

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