Bacille Calmette-Guérin vaccine reprograms human neonatal lipid metabolism in vivo and in vitro.

Bacille Calmette-Guérin vaccine reprograms human neonatal lipid metabolism in vivo and in vitro.
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卡介苗在体内和体外重新编程人类新生儿脂质代谢。

DOI:
10.1016/j.celrep.2022.110772
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发表时间:
2022-05-03
期刊:
影响因子:
8.8
通讯作者:
Levy, Ofer
Levy, Ofer
中科院分区:
生物学1区
文献类型:
--
作者:
Diray-Arce, Joann;Angelidou, Asimenia;Jensen, Kristoffer Jarlov;Conti, Maria Giulia;Kelly, Rachel S.;Pettengill, Matthew A.;Liu, Mark;van Haren, Simon D.;McCulloch, Scott D.;Michelloti, Greg;Idoko, Olubukola;Consortium, Epic;Kollmann, Tobias R.;Kampmann, Beate;Steen, Hanno;Al Ozonoff;Lasky-Su, Jessica;Benn, Christine S.;Levy, Ofer

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疫苗的开发通常对其分子影响的了解有限。虽然系统疫苗学能够表征作用机制,但这些工具尚未应用于感染风险高且接种疫苗最多的婴儿。卡介苗通过尚不完全了解的机制保护婴儿免受播散性结核病和与结核病无关的感染。我们采用基于质谱的血浆代谢组学来分析几内亚比绍体内和美国体外bcg诱导的婴儿反应。BCG诱导的溶血磷脂酰胆碱(LPCs)与tlr激动剂和纯化蛋白衍生物(PPD,分枝杆菌抗原)诱导的体外血液细胞因子产生相关,提高了LPCs参与BCG免疫原性的可能性。对冈比亚独立新生儿队列的分析表明,疫苗诱导的代谢物,如磷脂和鞘脂具有共通性。bcg诱导的血浆脂质组和LPCs的变化可能有助于其免疫原性,并为早期生命疫苗的开发提供信息。Diray-Arce等人报道,卡介苗接种在体内和体外改变了生命早期的血浆代谢组。他们还证明卡介苗血浆溶血磷脂的变化与tlr激动剂和分枝杆菌诱导的细胞因子和趋化因子反应相关。
Vaccines have generally been developed with limited insight into their molecular impact. While systems vaccinology enables characterization of mechanisms of action, these tools have yet to be applied to infants, who are at high risk of infection and receive the most vaccines. Bacille Calmette-Guérin (BCG) protects infants against disseminated tuberculosis (TB) and TB-unrelated infections via incompletely understood mechanisms. We employ mass-spectrometry-based metabolomics of blood plasma to profile BCG-induced infant responses in Guinea-Bissau in vivo and the US in vitro. BCG-induced lysophosphatidylcholines (LPCs) correlate with both TLR-agonist- and purified protein derivative (PPD, mycobacterial antigen)-induced blood cytokine production in vitro, raising the possibility that LPCs contribute to BCG immunogenicity. Analysis of an independent newborn cohort from The Gambia demonstrates shared vaccine-induced metabolites, such as phospholipids and sphingolipids. BCG-induced changes to the plasma lipidome and LPCs may contribute to its immunogenicity and inform the development of early life vaccines. Diray-Arce et al. report that BCG vaccination shifts the plasma metabolome early in life in vivo and in vitro. They also demonstrate that BCG changes in plasma lysophospholipids correlated with TLR-agonist- and mycobacterial-induced cytokine and chemokine responses.
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