Transiently heritable fates and quorum sensing drive early IFN-I response dynamics
- Technical University Eindhoven, Netherlands
- Eindhoven University of Technology, Netherlands
- University of Delaware, United States
Abstract
Type I Interferon (IFN-I)-mediated antiviral responses are central to host defense against viral infections. Crucial is the tight and well-orchestrated control of cellular decision-making leading to the production of IFN-Is. Innovative single-cell approaches revealed that the initiation of IFN-I production is limited to only fractions of 1-3% of the total population, both found in vitro, in vivo, and across cell types, which were thought to be stochastically regulated. To challenge this dogma, we addressed the influence of various stochastic and deterministic host-intrinsic factors on dictating early IFN-I responses, using a murine fibroblast reporter model. Epigenetic drugs influenced the percentage of responding cells. Next, with the classical Luria-Delbrück fluctuation test, we provided evidence for transient heritability driving responder fates, which was verified with mathematical modeling. Finally, while studying varying cell-densities, we substantiated an important role for cell density in dictating responsiveness, similar to the phenomenon of quorum sensing. Together, this systems immunology approach opens up new avenues to progress the fundamental understanding on cellular decision-making during early IFN-I responses, which can be translated to other (immune) signaling systems.
Data availability
The raw data supporting the conclusions of this article are available on DataDryad
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Raw Data TotalDryad Digital Repository, doi:10.5061/dryad.2547d7wtz.
Article and author information
Author details
Laura Christine Van Eyndhoven
Funding
European Research Council (802791)
- Jurjen Tel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Van Eyndhoven et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Transiently heritable fates and quorum sensing drive early IFN-I response dynamics
eLife 12:e83055.
https://doi.org/10.7554/eLife.83055
