Directional sensing and signal integration by immune cells

Human neutrophils and other immune cells sense chemical gradients to navigate to sites of injury, infection, and inflammation in the body. Impressively, these cells can detect gradients that differ by as little as about 1% in concentration across the length of the cell. Abstract models suggest that they may do this by integrating opposing local positive and long-range negative signals generated by receptors. However, the molecular basis for signal processing remains unclear. To investigate models of sensing, we developed experimental tools to control receptors with light while measuring downstream signaling responses with spatial resolution in single cells. We are directly measuring responses to both local and cell-wide receptor activation to determine the wiring of signal processing. While we do not see evidence for long-range negative signals, we do see a subcellular context-dependence of signal transmission. We propose that signal transmission from receptors happens locally, but cell-wide polarity biases sensing to maintain persistent migration and achieve temporal averaging to promote directional accuracy.