RT Journal Article
SR Electronic
T1 Transiently heritable fates and quorum sensing drive early IFN-I response dynamics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.09.11.507479
DO 10.1101/2022.09.11.507479
A1 Van Eyndhoven, Laura C.
A1 Verberne, Vincent P.G.
A1 Bouten, Carlijn V.C.
A1 Singh, Abhyudai
A1 Tel, Jurjen
YR 2022
UL http://biorxiv.org/content/early/2022/09/13/2022.09.11.507479.abstract
AB 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 only limited to a fraction of 1-3% of the total population, both found in vitro and in vivo, which were thought to be stochastically regulated. To challenge this dogma, we addressed the influence of various host-intrinsic factors, both stochastic and epigenetic, on dictating early IFN-I responses. Hypomethylating drugs increased the percentage of responding cells. Next, with the classical Luria-Delbrück fluctuation test, we provided evidence that the fate of becoming a responding cell is transiently heritable. Finally, while studying varying cell-densities, we substantiated an important role for quorum sensing, which was verified by mathematical modeling. Together, this systems immunology approach opens up new avenues to progress the fundamental understanding of cellular decision-making during early IFN-I responses, which can be translated to other (immune) signaling systems, and ultimately will improve IFN-I based immune therapies.Competing Interest StatementThe authors have declared no competing interest.