在生命早期使用抗生素会损害MAIT细胞介导免疫在成年后
Gabrielle R LeBlanc1,2, Adam L Sobel1,2, Jonathan Melamed1,2
1Department of Immunology and Microbiology, Scripps Research, La Jolla, CA, USA.
The Journal of experimental medicine
|December 16, 2025
概括
早期使用抗生素可以通过消耗肠道细菌来损害粘膜关联不变T细胞 (MAIT) 的发展. 这种损伤增加了对肺炎等感染的易感性.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 发展生物学 发展生物学
背景情况:
- 粘膜关联不变T细胞 (MAIT) 是在屏障组织中发现的关键免疫细胞.
- MAIT 细胞识别出由 рибофлавин合成产生的微生物代谢物.
- 生命早期的微生物暴露塑造了MAIT细胞种群.
研究的目的:
- 研究早期抗生素暴露对MAIT细胞发育的影响.
- 为了确定抗生素诱导的 riboflavin 合成 commensals 的耗尽是否会影响 MAIT 细胞的丰富性和功能.
- 评估MAIT细胞发育受损对宿主感染敏感性的影响.
主要方法:
- 鉴定消耗利博夫拉合成共生体的抗生素.
- 在小鼠的关键早期生命窗口期间给予抗生素.
- 评估MAIT细胞数量和对肺炎的敏感性.
- 与MAIT细胞缺乏的小鼠进行比较,并通过共生给药进行救援实验.
主要成果:
- 在特定的生命早期时期服用抗生素会损害MAIT细胞的发育.
- 减少MAIT细胞丰度导致小鼠对肺炎的易感性增加.
- 缺少MAIT细胞的小鼠对生命早期的抗生素效应没有敏感.
- 在抗生素治疗期间恢复 riboflavin-synthesizing commensals 挽救了 MAIT 细胞发育和免疫力.
结论:
- 生命早期必不可少的肠道细菌的暂时耗尽可以永久影响MAIT细胞的发育.
- 由于早年暴露于抗生素,MAIT细胞免疫力受损可能会增加对感染的易感性.
- 恢复特定的共生细胞可以减轻抗生素对MAIT细胞发育的不良影响.
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