Rapidly dynamic host cell heterogeneity in bacterial adhesion governs susceptibility to infection by Listeria monocytogenes

Interactions between host cells and individual pathogenic bacteria determine the clinical severity of disease during systemic infection in humans. Vascular endothelial cells, which line the lumen of blood vessels, represent a critical barrier for a bacterium in the bloodstream. These cells adopt a myriad of phenotypes that may modulate their susceptibility to infection; however, the precise determinants of their heterogeneity in susceptibility are not known. Here, we show that heterogeneity in susceptibility to Listeria monocytogenes infection among primary human vascular endothelial cells can be attributed entirely to robust, preexisting host cell heterogeneity in bacterial adhesion, and we find no evidence for significant heterogeneity in later steps of infection. High susceptibility to adhesion decays rapidly, within 30–60 min. Thus, rapidly fluctuating, nongenetic variability in bacterial adhesion diversifies susceptibility to infection, both among host cells and within individual cells over time.