在生命早期使用抗生素随后会损害MAIT细胞介导免疫力
bioRxiv : the preprint server for biology
|May 27, 2024
概括
早期使用抗生素可能会损害粘膜关联不变T细胞 (MAIT) 的发展,这对免疫防御至关重要. 在治疗期间恢复肠道细菌可以恢复MAIT细胞免疫力.
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重要免疫细胞.
- MAIT细胞从利博黄素合成中识别微生物代谢物,影响它们的早期生命发展.
- 在关键发育窗口期间接触抗生素可能会破坏MAIT细胞的丰富性和功能.
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:
- 识别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细胞发育和抗生素治疗后的丰度.
- 在抗生素治疗和MAIT细胞缺乏的小鼠中评估宿主对肺炎的易感性.
- 恢复MAIT细胞发育通过同时服用初生药物.
主要成果:
- 早期使用抗生素会损害MAIT细胞的发育,因为它会减少合成利博弗拉的细胞.
- 减少MAIT细胞丰度导致小鼠对肺炎的易感性增加.
- 在MAIT细胞缺乏的小鼠中,在生命早期服用抗生素后,对肺炎的敏感性没有增加.
- 同时服用合成利博弗拉的共生药物恢复了MAIT细胞的发育和免疫力.
结论:
- 早期抗生素诱导的特定肠道微生物的枯竭对MAIT细胞成熟产生不利影响.
- 这种干扰可能会损害免疫系统对抗后续感染的能力.
- 针对性地恢复共生细菌提供了一个潜在的策略,以减轻抗生素诱导的免疫失调.
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