Transiently heritable fates and quorum sensing drive early IFN-I response dynamics

  1. Laura Christine Van Eyndhoven
  2. Vincent PG Verberne
  3. Carlijn VC Bouten
  4. Abhyudai Singh
  5. Jurjen Tel  Is a corresponding author
  1. Technical University Eindhoven, Netherlands
  2. Eindhoven University of Technology, Netherlands
  3. 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

The following data sets were generated
    1. Van Eyndhoven LC
    (2023) Raw Data Total
    Dryad Digital Repository, doi:10.5061/dryad.2547d7wtz.

Article and author information

Author details

  1. Laura Christine Van Eyndhoven

    Department of Biomedical Engineering, Technical University Eindhoven, Eindhoven, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7230-1134
  2. Vincent PG Verberne

    Department of Biomedical Engineering, Technical University Eindhoven, Eindhoven, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Carlijn VC Bouten

    Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Abhyudai Singh

    Department of Electrical and Computer Engineering, University of Delaware, Delaware, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1451-2838
  5. Jurjen Tel

    Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands
    For correspondence
    j.tel@tue.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7213-3422

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.

Reviewing Editor

  1. Ahmad S Khalil, Boston University, United States

Publication history

  1. Received: August 30, 2022
  2. Accepted: January 10, 2023
  3. Accepted Manuscript published: January 11, 2023 (version 1)

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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  1. Laura Christine Van Eyndhoven
  2. Vincent PG Verberne
  3. Carlijn VC Bouten
  4. Abhyudai Singh
  5. Jurjen Tel
(2023)
Transiently heritable fates and quorum sensing drive early IFN-I response dynamics
eLife 12:e83055.
https://doi.org/10.7554/eLife.83055

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