Creative artwork featuring 3D renderings of respiratory syncytial virus (the viral envelope is purple, G- glycoproteins are light blue, and F-glycoproteins are orange). F-glycoproteins allow the virus to fuse with and infect human cells. Image credit: NIAID (CC BY 2.0)
When we start to develop a cold, influenza or another viral infection, some of our cells produce signaling molecules known as type I interferons (or IFN-Is for short). These early IFN-I signals establish defenses against viruses in both infected and as yet uninfected cells. If the cells produce too much IFN-Is, however, it can result in uncontrolled inflammation that may harm the body and cause life threatening illness.
Individual cells need to tightly control how much IFN-Is they produce and match this with the course of the viral infection. They also need to assess how much IFN-I their neighbors are producing and adjust their behavior accordingly.
Cells have evolved a myriad of mechanisms to ensure the right amounts of IFN-Is are produced in different circumstances. Broadly, these mechanisms can be divided into two categories: stochastic regulation and deterministic regulation. Stochastic regulation occurs when individual cells receive the exact same information, but this leads to different outcomes, such as, different cells producing various quantities of IFN-Is. In contrast, deterministic regulation causes the same outcome in different cells independent on the information they receive.
It was thought that stochastic regulation is the main driver of early IFN-1 responses, but recently a handful of studies have reported deterministic regulation being primarily responsible, instead. Here, Van Eyndhoven et al. explored the roles of both types of regulation in the early IFN-I responses of mouse cells.
Van Eyndhoven et al. used genetic approaches and mathematical modelling to show that the fraction of cells that initiate early IFN-I responses can be considered deterministic. Moreover, this deterministic feature turned out to be heritable, such that the fate to produce IFN-I gets passed on for several generations of cells. Additionally, the experiments suggest that cell density, that is, how tightly packed together the cells are, plays an important role in controlling how many cells make IFN-I, with a lower cell density resulting in a higher fraction of cells producing IFN-Is.
The findings of Van Eyndhoven et al. add to a growing body of evidence reporting heritable states that can guide decision-making in individual cells. Furthermore, it revises our view on how individual immune cells coordinate population-wide responses.
