Early microbial exposure shapes adult immunity by altering CD8+ T cell development.
Early microbial exposure shapes adult immunity by altering CD8+ T cell development.
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DOI：
10.1073/pnas.2212548119
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发表时间：
2022-12-06
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
生命早期的微生物暴露可能对健康产生长期影响。然而，我们对微生物环境如何塑造后代免疫系统的理解是不完整的。在这份报告中，我们发现胎儿来源的CD8+ T细胞的比例和功能被早期微生物环境改变。这些变化持续到成年期，并影响免疫易感性细胞内病原体。我们的研究结果为微生物暴露如何导致免疫反应的个体差异提供了关键见解，这表明我们可能能够根据成人免疫系统中胎儿与成人来源的CD8+ T细胞的比例预测感染结果和疾病风险。在发育过程中接触微生物会对个体的健康产生长期影响。然而，早期生命中的微生物暴露如何导致免疫系统的永久性变化尚不清楚。在这里，我们表明微生物环境通过改变CD8+ T细胞区室的发育结构来改变免疫易感性的设定点。特别是，早期微生物暴露导致高度反应性的胎儿来源的CD8+ T细胞的优先扩增，这些细胞持续到成年期，并为宿主提供增强的针对细胞内病原体的免疫保护。有趣的是，胎儿来源的CD8+ T细胞的微生物教育发生在胸腺发育过程中，而不是在外周，并涉及获得更像效应器的表观遗传程序。总的来说，我们的研究结果提供了一个概念框架，用于理解早期生命中的微生物定植如何导致免疫系统的终身变化。
Microbial exposure in early life can have long-term consequences on health. However, our understanding of how the microbial environment shapes the offspring’s immune system is incomplete. In this report, we found that the proportion and function of fetal-derived CD8+ T cells are altered by the early microbial environment. These changes persist into adulthood and affect immune susceptibility to intracellular pathogens. Our findings provide key insights into how microbial exposure leads to individual variation in immune responsiveness, suggesting that we may be able to predict infection outcomes and disease risk based on the ratio of fetal- to adult-derived CD8+ T cells present in the adult immune system. Microbial exposure during development can elicit long-lasting effects on the health of an individual. However, how microbial exposure in early life leads to permanent changes in the immune system is unknown. Here, we show that the microbial environment alters the set point for immune susceptibility by altering the developmental architecture of the CD8+ T cell compartment. In particular, early microbial exposure results in the preferential expansion of highly responsive fetal-derived CD8+ T cells that persist into adulthood and provide the host with enhanced immune protection against intracellular pathogens. Interestingly, microbial education of fetal-derived CD8+ T cells occurs during thymic development rather than in the periphery and involves the acquisition of a more effector-like epigenetic program. Collectively, our results provide a conceptual framework for understanding how microbial colonization in early life leads to lifelong changes in the immune system.
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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
DOI：
10.1084/jem.20081829
发表时间：
2009-02-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Haluszczak C;Akue AD;Hamilton SE;Johnson LD;Pujanauski L;Teodorovic L;Jameson SC;Kedl RM
通讯作者：
Kedl RM
影响因子：
64.8
作者：
Bateson, P;Barker, D;Sultan, SE
通讯作者：
Sultan, SE
影响因子：
14.2
作者：
Ege, Markus Johannes;Herzum, Ileana;von Mutius, Erika
通讯作者：
von Mutius, Erika
影响因子：
64.5
作者：
IKUTA, K;KINA, T;WEISSMAN, IL
通讯作者：
WEISSMAN, IL