Institute for Computational Medicine, NYU Grossman School of Medicine, New York, NY, USA.
Department of Microbiology, NYU Grossman School of Medicine, New York, NY, USA.
Cell Rep. 2022 Oct 11;41(2):111477. doi: 10.1016/j.celrep.2022.111477.
Innate immune recognition of bacterial pathogens is a key determinant of the ensuing systemic response, and host or pathogen heterogeneity in this early interaction can impact the course of infection. To gain insight into host response heterogeneity, we investigate macrophage inflammatory dynamics using primary human macrophages infected with Group B Streptococcus. Transcriptomic analysis reveals discrete cellular states within responding macrophages, one of which consists of four sub-states, reflecting inflammatory activation. Infection with six additional bacterial species-Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, Yersinia pseudotuberculosis, Shigella flexneri, and Salmonella enterica-recapitulates these states, though at different frequencies. We show that modulating the duration of infection and the presence of a toxin impacts inflammatory trajectory dynamics. We provide evidence for this trajectory in infected macrophages in an in vivo model of Staphylococcus aureus infection. Our cell-state analysis defines a framework for understanding inflammatory activation dynamics in response to bacterial infection.
先天免疫识别细菌病原体是后续全身反应的关键决定因素，宿主或病原体在这种早期相互作用中的异质性会影响感染的进程。为了深入了解宿主反应的异质性，我们使用原代人巨噬细胞感染 B 群链球菌来研究巨噬细胞炎症动力学。转录组分析揭示了反应性巨噬细胞中的离散细胞状态，其中一种状态由四个亚状态组成，反映了炎症激活。感染另外六种细菌物种-金黄色葡萄球菌、李斯特菌、粪肠球菌、假结核耶尔森菌、福氏志贺菌和肠炎沙门氏菌-再现了这些状态，但频率不同。我们表明，调节感染持续时间和毒素的存在会影响炎症轨迹动力学。我们在金黄色葡萄球菌感染的体内模型中为感染巨噬细胞中的这种轨迹提供了证据。我们的细胞状态分析为理解细菌感染后炎症激活动力学提供了一个框架。
