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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Antiviral responses in mouse embryonic stem cells: differential development of cellular mechanisms in type I
Ruoxing Wang1, Jundi Wang1, Dhiraj Acharya1
1From the Departments of Biological Sciences and.
Abstract:
We have recently reported that mouse embryonic stem cells (mESCs) are deficient in expressing type I interferons (IFNs) in response to viral infection and synthetic viral RNA analogs (Wang, R., Wang, J., Paul, A. M., Acharya, D., Bai, F., Huang, F., and Guo, Y. L. (2013) J. Biol. Chem. 288, 15926-15936). Here, we report that mESCs are able to respond to type I IFNs, express IFN-stimulated genes, and mediate the antiviral effect of type I IFNs against La Crosse virus and chikungunya virus. The major signaling components in the IFN pathway are expressed in mESCs. Therefore, the basic molecular mechanisms that mediate the effects of type I IFNs are functional in mESCs; however, these mechanisms may not yet be fully developed as mESCs express lower levels of IFN-stimulated genes and display weaker antiviral activity in response to type I IFNs when compared with fibroblasts. Further analysis demonstrated that type I IFNs do not affect the stem cell state of mESCs. We conclude that mESCs are deficient in type I IFN expression, but they can respond to and mediate the cellular effects of type I IFNs. These findings represent unique and uncharacterized properties of mESCs and are important for understanding innate immunity development and ESC physiology.
Insights
Mouse embryonic stem cells (mESCs) do not produce type I interferons (IFNs) but can respond to them. This study reveals unique properties of mESCs in innate immunity and stem cell physiology.
Area of Science:
- Immunology
- Developmental Biology
- Stem Cell Biology
Background:
- Mouse embryonic stem cells (mESCs) were previously found deficient in type I interferon (IFN) expression upon viral stimulation.
- Understanding the innate immune response in stem cells is crucial for developmental biology and regenerative medicine.
Purpose of the Study:
- To investigate the responsiveness of mESCs to type I IFNs.
- To determine if mESCs can mediate antiviral effects.
- To assess the impact of type I IFNs on the stem cell state.
Main Methods:
- Stimulation of mESCs with type I IFNs.
- Analysis of IFN-stimulated gene expression.
- Assessment of antiviral activity against La Crosse virus and chikungunya virus.
- Evaluation of stem cell marker expression.
Main Results:
- mESCs express key IFN pathway signaling components.
- mESCs respond to type I IFNs by expressing IFN-stimulated genes and mediating antiviral effects.
- mESCs exhibit weaker IFN responses compared to fibroblasts.
- Type I IFNs do not alter the stem cell state of mESCs.
Conclusions:
- mESCs are deficient in type I IFN expression but possess functional IFN response pathways.
- mESCs can respond to type I IFNs, exhibiting antiviral activity without compromising their stem cell identity.
- These findings highlight unique characteristics of mESCs relevant to innate immunity and stem cell biology.
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