Spatiotemporal NF-κB dynamics encodes the position, amplitude, and duration of local immune inputs

Infected cells communicate through secreted signaling molecules like cytokines, which carry information about pathogens. How differences in cytokine secretion affect inflammatory signaling over space and how responding cells decode information from propagating cytokines are not understood. By computationally and experimentally studying NF-κB dynamics in cocultures of signal-sending cells (macrophages) and signal-receiving cells (fibroblasts), we find that cytokine signals are transmitted by wave-like propagation of NF-κB activity and create well-defined activation zones in responding cells. NF-κB dynamics in responding cells can simultaneously encode information about cytokine dose, duration, and distance to the cytokine source. Spatially resolved transcriptional analysis reveals that responding cells transmit local cytokine information to distance-specific proinflammatory gene expression patterns, creating "gene expression zones."Despite single-cell variability, the size and duration of the signaling zone are tightly controlled by the macrophage secretion profile. Our results highlight how macrophages tune cytokine secretion to control signal transmission distance and how inflammatory signaling interprets these signals in space and time.

All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. RNA sequencing data have been deposited at NCBI Gene Expression Omnibus (GEO) database (GSE189062) and are publicly available as of the date of publication. Single-cell NF-κB dynamics for all experiments and codes for heatmaps and single-cell dynamics have been deposited in Zenodo (DOI: 10.5281/zenodo.6858118) and are publicly available as of the date of publication. The codes for the MDS plot and clustering of RNA sequencing data have been deposited in the same Zenodo repository.