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High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
Stochastic receptor expression determines cell fate upon interferon treatment
Doron Levin1, Daniel Harari, Gideon Schreiber
1Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Molecular and Cellular Biology
|June 22, 2011
Summary
Type I interferons activate cells via a common receptor. Cell response, like antiviral states or apoptosis, depends on stochastic receptor levels, with low numbers ensuring robust antiviral defense and high numbers enabling fine-tuned antiproliferative effects.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Type I interferons (IFNs) induce varied cellular responses through the IFNAR1/IFNAR2 receptor complex.
- While antiviral states are universal, antiproliferative and apoptotic effects are cell-specific, even at saturating IFN concentrations.
Purpose of the Study:
- To investigate the role of cell surface receptor expression levels in mediating differential Type I IFN responses.
- To elucidate the quantitative relationship between IFN receptor numbers and downstream signaling outcomes.
Main Methods:
- Utilized small interfering RNA (siRNA) to modulate IFN receptor expression levels.
- Assessed cellular responses including antiviral state activation, antiproliferative activity, apoptosis, STAT activation, and gene induction.
- Employed a tight-binding IFN variant to differentiate receptor number effects from binding affinity.
Main Results:
- Reduced IFN receptor numbers decreased the fraction of responsive cells, independent of IFN type or binding affinity.
- Lower receptor counts increased EC50 for IFN-α2 but not for a tight-binding variant.
- A direct correlation was observed between receptor numbers, STAT activation, and gene induction levels.
Conclusions:
- Cellular response to Type I IFNs is a binary outcome determined by stochastic receptor expression levels.
- A minimal receptor threshold ensures a robust antiviral response common to all cells.
- Higher receptor expression is necessary for antiproliferative effects, allowing for single-cell level fine-tuning.
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