The tempo and mode of gene regulatory programs during bacterial infection.
The tempo and mode of gene regulatory programs during bacterial infection.
复制标题
细菌感染期间基因调节程序的克里思和模式。
DOI：
10.1016/j.celrep.2022.111477
复制
发表时间：
2022-10-11
期刊：
影响因子：
8.8
通讯作者：
Yanai, Itai
中科院分区：
文献类型：
--
作者：
Avital, Gal;Kuperwaser, Felicia;Pountain, Andrew W.;Lacey, Keenan A.;Zwack, Erin E.;Podkowik, Magdalena;Shopsin, Bo;Torres, Victor J.;Yanai, Itai
对细菌病原体的天然免疫识别是随后的全身反应的关键决定因素，而宿主或病原体在这种早期相互作用中的异质性可以影响感染过程。为了深入了解宿主反应的异质性，我们使用感染B组链球菌的原代人巨噬细胞来研究巨噬细胞的炎症动力学。转录分析揭示了反应巨噬细胞内离散的细胞状态，其中一种状态由四个亚状态组成，反映了炎症激活。另外六种细菌-金黄色葡萄球菌、单核细胞增生性李斯特菌、粪肠球菌、假结核耶尔森菌、福氏志贺菌和肠沙门氏菌-感染这些状态，尽管频率不同。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提供了感染巨噬细胞这一轨迹的证据。我们的细胞状态分析定义了一个框架，用于了解细菌感染时的炎症激活动力学。阿维塔尔等人。表明细菌感染诱导巨噬细胞处于离散的转录转录状态，这些状态对应于不同的反应功能。其中一种状态捕获了炎症激活，其特征是四个基因模块。细菌刺激、感染持续时间和毒素的存在会影响这种炎症轨迹的动态变化。
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. Avital et al. show that bacterial infection induces discrete transcriptomic states in macrophages that correspond to different response functions. One of these states captures inflammatory activation characterized by four gene modules. The dynamics of this inflammatory trajectory can be impacted by modulation of bacterial stimulus, infection duration, and presence of toxins.
登录
查看更多内容
影响因子：
14.9
作者：
Howe KL;Achuthan P;Allen J;Allen J;Alvarez-Jarreta J;Amode MR;Armean IM;Azov AG;Bennett R;Bhai J;Billis K;Boddu S;Charkhchi M;Cummins C;Da Rin Fioretto L;Davidson C;Dodiya K;El Houdaigui B;Fatima R;Gall A;Garcia Giron C;Grego T;Guijarro-Clarke C;Haggerty L;Hemrom A;Hourlier T;Izuogu OG;Juettemann T;Kaikala V;Kay M;Lavidas I;Le T;Lemos D;Gonzalez Martinez J;Marugán JC;Maurel T;McMahon AC;Mohanan S;Moore B;Muffato M;Oheh DN;Paraschas D;Parker A;Parton A;Prosovetskaia I;Sakthivel MP;Salam AIA;Schmitt BM;Schuilenburg H;Sheppard D;Steed E;Szpak M;Szuba M;Taylor K;Thormann A;Threadgold G;Walts B;Winterbottom A;Chakiachvili M;Chaubal A;De Silva N;Flint B;Frankish A;Hunt SE;IIsley GR;Langridge N;Loveland JE;Martin FJ;Mudge JM;Morales J;Perry E;Ruffier M;Tate J;Thybert D;Trevanion SJ;Cunningham F;Yates AD;Zerbino DR;Flicek P
通讯作者：
Flicek P
影响因子：
9.3
作者：
Cheng CS;Behar MS;Suryawanshi GW;Feldman KE;Spreafico R;Hoffmann A
通讯作者：
Hoffmann A
影响因子：
3.1
作者：
Feezor, RJ;Oberholzer, C;Oberholzer, A
通讯作者：
Oberholzer, A
影响因子：
3.8
作者：
BJORK, L;ANDERSSON, J;ANDERSSON, U
通讯作者：
ANDERSSON, U
影响因子：
9.3
作者：
Blecher-Gonen, Ronnie;Bost, Pierre;Amit, Ido
通讯作者：
Amit, Ido