Summary

Type I interferon (IFN) is a key driver of immunity to infections and cancer. Plasmacytoid dendritic cells (pDCs) are uniquely equipped to produce large quantities of type I IFN but the mechanisms that control this process are poorly understood. Here we report on a droplet-based microfluidic platform to investigate type I IFN production in human pDCs at the single-cell level. We show that type I IFN but not TNFα production is limited to a small subpopulation of individually stimulated pDCs and controlled by stochastic gene regulation. Combining single-cell cytokine analysis with single-cell RNA-seq profiling reveals no evidence for a pre-existing subset of type I IFN-producing pDCs. By modulating the droplet microenvironment, we demonstrate that vigorous pDC population responses are driven by a type I IFN amplification loop. Our study highlights the significance of stochastic gene regulation and suggests strategies to dissect the characteristics of immune responses at the single-cell level.

Overall design

Examination of the transcriptional profiles from single human plasmacytoid dendritic cells that were stimulated with CpG-C

Contributors

Florian Wimmers 1 2, Nikita Subedi 3 4, Nicole van Buuringen 1, Daan Heister 1, Judith Vivié 5, Inge Beeren-Reinieren 1, Rob Woestenenk 6, Harry Dolstra 6, Aigars Piruska 7, Joannes F M Jacobs 8, Alexander van Oudenaarden 5, Carl G Figdor 1, Wilhelm T S Huck 7, I Jolanda M de Vries 1, Jurjen Tel 9 10 11

Contact

J.Tel@tue.nl.(Jurjen Tel)