ACHOO!-trophils? Why some individuals come down with a cold in any given year, whereas others are spared, is poorly understood. Habibi et al. exposed volunteers to respiratory syncytial virus (RSV), one of the pathogens responsible for the common cold, and then followed them over the ensuing 2 weeks (see the Perspective by Mirchandani and Walmsley). The main factor distinguishing the infected from the noninfected was that the former showed signs of airway neutrophil activation before exposure to RSV. Conversely, protected individuals showed enhanced interleukin-17 signaling soon after virus inoculation. Similarly, mice pretreated with a neutrophil chemoattractant were more susceptible to RSV infection and CD8 + T cell–driven disease. Neutrophil proteases, which can modulate cytokine activity, may explain the disparity and could provide therapeutic targets for RSV and other respiratory infections. Science , this issue p. eaba9301 ; see also p. 166