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Modulation of bacterial metabolism by the microenvironment controls MAIT cell stimulation.
Mucosal Immunology ( IF 8 ) Pub Date : 2018-07-01 , DOI: 10.1038/s41385-018-0020-9
Mathias Schmaler 1 , Alessia Colone 2 , Julian Spagnuolo 1 , Michael Zimmermann 3, 4 , Marco Lepore 1 , Artem Kalinichenko 1 , Sumedha Bhatia 2 , Fabien Cottier 2 , Tobias Rutishauser 1 , Norman Pavelka 2 , Adrian Egli 5, 6 , Elisa Azzali 7 , Marco Pieroni 7 , Gabriele Costantino 7 , Petr Hruz 8 , Uwe Sauer 3 , Lucia Mori 1, 2 , Gennaro De Libero 1, 2
Affiliation  

Mucosal-associated invariant T (MAIT) cells are abundant innate-like T lymphocytes in mucosal tissues and recognize a variety of riboflavin-related metabolites produced by the microbial flora. Relevant issues are whether MAIT cells are heterogeneous in the colon, and whether the local environment influences microbial metabolism thereby shaping MAIT cell phenotypes and responses. We found discrete MAIT cell populations in human colon, characterized by the diverse expression of transcription factors, cytokines and surface markers, indicative of activated and precisely controlled lymphocyte populations. Similar phenotypes were rare among circulating MAIT cells and appeared when circulating MAIT cells were stimulated with the synthetic antigens 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil, and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil. Furthermore, bacteria grown in colon-resembling conditions with low oxygen tension and harvested at stationary growth phase, potently activated human MAIT cells. The increased activation correlated with accumulation of the above antigenic metabolites as indicated by mass spectrometry. Thus, the colon environment contributes to mucosal immunity by directly affecting bacterial metabolism, and indirectly controlling the stimulation and differentiation of MAIT cells.

中文翻译:

微环境对细菌代谢的调节控制着 MAIT 细胞的刺激。

粘膜相关不变 T (MAIT) 细胞是粘膜组织中丰富的先天样 T 淋巴细胞,可识别微生物菌群产生的多种核黄素相关代谢物。相关问题是 MAIT 细胞在结肠中是否异质,以及局部环境是否影响微生物代谢从而塑造 MAIT 细胞表型和反应。我们在人类结肠中发现了离散的 MAIT 细胞群,其特征是转录因子、细胞因子和表面标记的不同表达,表明淋巴细胞群被激活和精确控制。类似的表型在循环 MAIT 细胞中很少见,并且在用合成抗原 5-(2-oxoethylideneamino)-6-D-ribitelaminouracil 和 5-(2-oxopropylidenamino)-6-D-ribitylaminouracil 刺激循环 MAIT 细胞时出现。此外,在低氧张力的类似结肠的条件下生长并在稳定生长期收获的细菌有效激活了人类 MAIT 细胞。如质谱所示,增加的活化与上述抗原性代谢物的积累相关。因此,结肠环境通过直接影响细菌代谢并间接控制 MAIT 细胞的刺激和分化来促进粘膜免疫。
更新日期:2018-05-09
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