Trained Immunity Confers Broad-Spectrum Protection Against Bacterial Infections.
Trained Immunity Confers Broad-Spectrum Protection Against Bacterial Infections.
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DOI：
10.1093/infdis/jiz692
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发表时间：
2020-11-09
期刊：
影响因子：
--
通讯作者：
Roger T
中科院分区：
文献类型：
--
作者：
Ciarlo E;Heinonen T;Théroude C;Asgari F;Le Roy D;Netea MG;Roger T
先天免疫系统会回忆一次挑战以适应次要挑战，这种现象称为训练免疫。训练涉及细胞代谢、表观遗传和功能重编程，但经过广泛训练的免疫力如何防止感染尚不清楚。我们首次探讨了训练有素的免疫力是否可以在大量临床前感染模型中提供保护。对小鼠进行训练并使其遭受由金黄色葡萄球菌、单核细胞增生李斯特菌、大肠杆菌、啮齿类柠檬酸杆菌和铜绿假单胞菌引起的全身感染、腹膜炎、肠炎和肺炎。对血液、骨髓和器官中的细菌、细胞因子、白细胞和造血前体进行定量。使用耗尽或阻断方法研究了单核细胞/巨噬细胞、粒细胞和白细胞介素 1 信号传导的作用。在所有临床前模型中，诱导经过训练的免疫保护小鼠，包括在远处器官开始训练和感染时。训练有素的免疫力可增加骨髓造血祖细胞、血液中 Ly6C 高的炎症单核细胞和粒细胞，以及持续的血液抗菌反应。需要单核细胞/巨噬细胞和白细胞介素 1 信号传导来保护受过训练的小鼠免受李斯特菌病的侵害。经过训练的小鼠可以在长达 5 周的时间内有效地免受腹膜炎和李斯特菌病的侵害。经过训练的免疫力可提供广谱保护，防止致命细菌感染。这些观察结果支持开发经过训练的基于免疫的策略来改善宿主防御。我们使用临床前模型来证明，经过训练的免疫力可以提供广谱保护，防止细菌感染。训练有素的免疫增加了骨髓祖细胞和循环炎性单核细胞和中性粒细胞，单核细胞/巨噬细胞和白细胞介素1信号的消耗或中和损害了训练有素的免疫介导的保护。
The innate immune system recalls a challenge to adapt to a secondary challenge, a phenomenon called trained immunity. Training involves cellular metabolic, epigenetic and functional reprogramming, but how broadly trained immunity protects from infections is unknown. For the first time, we addressed whether trained immunity provides protection in a large panel of preclinical models of infections. Mice were trained and subjected to systemic infections, peritonitis, enteritis, and pneumonia induced by Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Citrobacter rodentium, and Pseudomonas aeruginosa. Bacteria, cytokines, leukocytes, and hematopoietic precursors were quantified in blood, bone marrow, and organs. The role of monocytes/macrophages, granulocytes, and interleukin 1 signaling was investigated using depletion or blocking approaches. Induction of trained immunity protected mice in all preclinical models, including when training and infection were initiated in distant organs. Trained immunity increased bone marrow hematopoietic progenitors, blood Ly6Chigh inflammatory monocytes and granulocytes, and sustained blood antimicrobial responses. Monocytes/macrophages and interleukin 1 signaling were required to protect trained mice from listeriosis. Trained mice were efficiently protected from peritonitis and listeriosis for up to 5 weeks. Trained immunity confers broad-spectrum protection against lethal bacterial infections. These observations support the development of trained immunity-based strategies to improve host defenses. We used preclinical models to demonstrate that trained immunity confers broad-spectrum protection against bacterial infections. Trained immunity increased myeloid progenitors and circulating inflammatory monocytes and neutrophils, and depletion or neutralization of monocytes/macrophages and interleukin 1 signaling impaired trained immunity-mediated protection.
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影响因子：
64.5
作者：
Mitroulis I;Ruppova K;Wang B;Chen LS;Grzybek M;Grinenko T;Eugster A;Troullinaki M;Palladini A;Kourtzelis I;Chatzigeorgiou A;Schlitzer A;Beyer M;Joosten LAB;Isermann B;Lesche M;Petzold A;Simons K;Henry I;Dahl A;Schultze JL;Wielockx B;Zamboni N;Mirtschink P;Coskun Ü;Hajishengallis G;Netea MG;Chavakis T
通讯作者：
Chavakis T
影响因子：
64.5
作者：
Bekkering, Siroon;Arts, Rob J. W.;Netea, Mihai G.
通讯作者：
Netea, Mihai G.
影响因子：
100.3
作者：
Farber, Donna L.;Netea, Mihai G.;Zinkernagel, Rolf M.
通讯作者：
Zinkernagel, Rolf M.
影响因子：
16.6
作者：
Buscher, Konrad;Wang, Huiyu;Song, Jian
通讯作者：
Song, Jian
影响因子：
29
作者：
Arts RJ;Novakovic B;Ter Horst R;Carvalho A;Bekkering S;Lachmandas E;Rodrigues F;Silvestre R;Cheng SC;Wang SY;Habibi E;Gonçalves LG;Mesquita I;Cunha C;van Laarhoven A;van de Veerdonk FL;Williams DL;van der Meer JW;Logie C;O'Neill LA;Dinarello CA;Riksen NP;van Crevel R;Clish C;Notebaart RA;Joosten LA;Stunnenberg HG;Xavier RJ;Netea MG
通讯作者：
Netea MG