During acute Trypanosoma cruzi infection highly susceptible mice deficient in natural killer cells are protected by a single α-galactosylceramide treatment
During acute Trypanosoma cruzi infection highly susceptible mice deficient in natural killer cells are protected by a single α-galactosylceramide treatment
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DOI：
10.1111/j.1365-2567.2006.02439.x
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发表时间：
2006-11-01
期刊：
影响因子：
6.4
通讯作者：
Kahn, Stuart J.
中科院分区：
文献类型：
--
作者：
Duthie, Malcolm S.;Kahn, Stuart J.
通过用自然杀伤（NK）T细胞糖脂抗原α-半乳糖神经酰胺（α-GalCer）治疗来改善针对克氏锥虫的保护性免疫应答。在T. Cruzi感染降低寄生虫血症和寄生虫存活率。这种保护依赖于CD 1d限制性NKT细胞和干扰素-γ（IFN-γ），表明α-GalCer激活的NKT细胞产生IFN-γ，其刺激细胞的先天性和适应性免疫应答以提供保护。为了了解哪些细胞提供保护，我们在这里研究了α-GalCer治疗缺乏不同免疫细胞的小鼠。令人惊讶的是，尽管NK细胞提供了针对T. cruzi，并且是α-GalCer处理后IFN-γ的主要来源，因此α-GalCer诱导的保护不需要NK细胞。对NK细胞耗竭小鼠的α-GalCer治疗控制了寄生虫血症并防止了死亡。相反，需要吞噬细胞、辅助性T细胞和细胞毒性T细胞。此外，α-GalCer治疗MHC II-/-或CD 8 α（-/-）小鼠加重了感染，表明α-GalCer治疗诱导了一些有利于寄生虫的反应。总之，α-GalCer对T. cruzi需要多种细胞应答，但不需要NK细胞应答。这些结果提供了有用的信息，因为α-GalCer正在开发用于治疗感染，自身免疫性疾病，过敏和癌症。
The protective immune response against Trypanosoma cruzi is improved by treatment with the natural killer (NK) T-cell glycolipid antigen alpha-galactosylceramide (alpha-GalCer). A single alpha-GalCer treatment of mice before T. cruzi infection decreases parasitaemia and prolongs survival. This protection is dependent on CD1d-restricted NKT cells and interferon-gamma (IFN-gamma) suggesting that alpha-GalCer-activated NKT cells produce IFN-gamma, which stimulates the cells of the innate and adaptive immune responses to provide protection. To learn which cells provide protection we investigate here alpha-GalCer treatment of mice deficient in different immune cells. Surprisingly, although NK cells provide protection against T. cruzi, and are a major source of IFN-gamma following alpha-GalCer treatment, NK cells are not required for the alpha-GalCer-induced protection. The alpha-GalCer treatment of NK-cell-depleted mice controlled parasitaemia and prevented death. In contrast, phagocytes, helper T cells and cytotoxic T cells are required. Furthermore, alpha-GalCer treatment of MHC II-/- or CD8 alpha(-/-) mice exacerbated the infection, demonstrating that alpha-GalCer treatment induces some responses that favour the parasite. In summary alpha-GalCer protection against T. cruzi required multiple cellular responses, but not the response of NK cells. These results provide useful information because alpha-GalCer is being developed as therapy for infections, autoimmune diseases, allergy and cancers.