Transiently heritable fates and quorum sensing drive early IFN-I response dynamics
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 pro...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-01-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/83055 |
| _version_ | 1811168044062343168 |
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| author | Laura C Van Eyndhoven Vincent PG Verberne Carlijn VC Bouten Abhyudai Singh Jurjen Tel |
| author_facet | Laura C Van Eyndhoven Vincent PG Verberne Carlijn VC Bouten Abhyudai Singh Jurjen Tel |
| author_sort | Laura C Van Eyndhoven |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T16:20:34Z |
| format | Article |
| id | doaj.art-b3d5f3a727584ff3aa34dc6d65e9fdab |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-10T16:20:34Z |
| publishDate | 2023-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b3d5f3a727584ff3aa34dc6d65e9fdab2023-02-09T15:38:33ZengeLife Sciences Publications LtdeLife2050-084X2023-01-011210.7554/eLife.83055Transiently heritable fates and quorum sensing drive early IFN-I response dynamicsLaura C Van Eyndhoven0https://orcid.org/0000-0001-7230-1134Vincent PG Verberne1Carlijn VC Bouten2Abhyudai Singh3https://orcid.org/0000-0002-1451-2838Jurjen Tel4https://orcid.org/0000-0002-7213-3422Laboratory of Immunoengineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, NetherlandsLaboratory of Immunoengineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, NetherlandsInstitute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, Netherlands; Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, NetherlandsDepartment of Electrical and Computer Engineering, University of Delaware, Newark, United StatesLaboratory of Immunoengineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, NetherlandsType 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.https://elifesciences.org/articles/83055cellular decision-makingepigeneticsinterferonsquorum sensingstochasticity |
| spellingShingle | Laura C Van Eyndhoven Vincent PG Verberne Carlijn VC Bouten Abhyudai Singh Jurjen Tel Transiently heritable fates and quorum sensing drive early IFN-I response dynamics eLife cellular decision-making epigenetics interferons quorum sensing stochasticity |
| title | Transiently heritable fates and quorum sensing drive early IFN-I response dynamics |
| title_full | Transiently heritable fates and quorum sensing drive early IFN-I response dynamics |
| title_fullStr | Transiently heritable fates and quorum sensing drive early IFN-I response dynamics |
| title_full_unstemmed | Transiently heritable fates and quorum sensing drive early IFN-I response dynamics |
| title_short | Transiently heritable fates and quorum sensing drive early IFN-I response dynamics |
| title_sort | transiently heritable fates and quorum sensing drive early ifn i response dynamics |
| topic | cellular decision-making epigenetics interferons quorum sensing stochasticity |
| url | https://elifesciences.org/articles/83055 |
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