产生IFNγ的iNKT细胞限制大肠中减毒活衣原体口服疫苗的效果
IFNγ-producing iNKTs restrict a live-attenuated chlamydia oral vaccine in the large intestine.
摘要(中文译文)
持续排出活菌，并在结肠内接种后持续存在于大肠中，而减毒活衣原体口服疫苗intrOv——一种对IFNγ敏感的突变株——则不能如此。已证明由3型先天淋巴细胞（ILC3s）递送的IFNγ可阻断intrOv的排出。我们现在报道，淋巴细胞缺陷但ILCs功能正常的小鼠允许intrOv持续存在，揭示了淋巴细胞在防止intrOv持续存在中的关键作用。负责的淋巴细胞亚群是自然杀伤T细胞（NKTs），因为CD1d或β2m缺陷的小鼠均允许intrOv持续存在。我们进一步将负责细胞缩小至产生IFNγ的恒定NKTs（iNKTs），因为TCRα J18片段（Traj18）、T-bet或IFNγ缺陷的小鼠均未能防止intrOv持续存在。一致地，intrOv诱导了IFNγ⁺iNKTs，而野生型iNKTs在淋巴细胞或IFNγ缺陷的小鼠中防止了intrOv持续存在。因此，IFNγ⁺iNKTs对于防止intrOv持续存在既是必要的也是充分的，而IFNγ⁺ILC3s则负责阻断intrOv排出，揭示了IFNγ⁺iNKTs与IFNγ⁺ILC3s在调控专性细胞内衣原体与宿主黏膜组织相互作用中的分工。该信息对于提高intrOv作为口服疫苗的安全性和有效性也至关重要。
Abstract
continuously sheds live organisms and persists in the large intestine following intracolonic inoculation, while the live-attenuated chlamydia oral vaccine intrOv, an IFNγ-susceptible mutant of , fails to do so. IFNγ delivered by group 3 innate lymphoid cells (ILC3s) have been shown to block intrOv shedding. We now report that mice deficient in lymphocytes but competent in ILCs allowed intrOv to persist, revealing a critical role of lymphocytes for preventing intrOv persistence. The responsible lymphocyte subsets are natural killer T cells (NKTs), as mice deficient in either CD1d or β2m permitted intrOv to persist. We further narrowed the responsible cells to invariant NKTs (iNKTs) that produce IFNγ, as mice deficient in TCRα J18 segment (Traj18), T-bet, or IFNγ failed to prevent intrOv persistence. Consistently, intrOv induced IFNγiNKTs, and wild-type iNKTs prevented intrOv persistence in mice deficient in either lymphocytes or IFNγ. Thus, IFNγiNKTs are both necessary and sufficient for preventing intrOv persistence, while IFNγILC3s are for blocking intrOv shedding, revealing a division of labor between IFNγiNKTs and IFNγILC3s in regulating the interaction of the obligate intracellular Chlamydia with host mucosal tissue. The information is also essential for improving the safety and efficacy of intrOv as an oral vaccine.
如何引用
AMA
Ahmed Mohamed Abdelsalam, Yi Wu, Mitchell Kronenberg, Huizhou Fan, Guangming Zhong. IFNγ-producing iNKTs restrict a live-attenuated chlamydia oral vaccine in the large intestine.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1851941.
APA
Ahmed Mohamed Abdelsalam, Yi Wu, Mitchell Kronenberg, Huizhou Fan, Guangming Zhong (2026). IFNγ-producing iNKTs restrict a live-attenuated chlamydia oral vaccine in the large intestine.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1851941
GB/T 7714
Ahmed Mohamed Abdelsalam, Yi Wu, Mitchell Kronenberg, Huizhou Fan, Guangming Zhong. IFNγ-producing iNKTs restrict a live-attenuated chlamydia oral vaccine in the large intestine.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1851941.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出