Department of Medicine, Massachusetts General Hospital, Boston, MA 02114.
Department of Biology, University of Washington, Seattle, WA 98185-1800.
Mol Biol Cell. 2020 Sep 1;31(19):2097-2106. doi: 10.1091/mbc.E19-08-0454. Epub 2020 Jun 17.
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 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.
宿主细胞与单个致病菌之间的相互作用决定了人类全身感染期间疾病的临床严重程度。血管内皮细胞排列在血管腔的内表面，是血液中细菌的一个关键屏障。这些细胞表现出多种表型，可能调节其对感染的易感性；然而，它们对感染易感性的异质性的确切决定因素尚不清楚。在这里，我们表明，原发性人血管内皮细胞对感染的易感性的异质性可以完全归因于细菌粘附中存在的强大的、预先存在的宿主细胞异质性，并且我们没有发现感染后期存在显著异质性的证据。对粘附的高易感性迅速衰减，在 30-60 分钟内。因此，细菌粘附的快速波动、非遗传变异性使感染的易感性在宿主细胞之间以及单个细胞内随时间多样化。
