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对鼠类皮肤共生菌的适应性免疫。

Adaptive immunity to murine skin commensals.

机构信息

Laboratory of Immunoregulation and.

Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814.

出版信息

Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):E2977-86. doi: 10.1073/pnas.1401820111. Epub 2014 Jul 7.

Abstract

The adaptive immune system provides critical defense against pathogenic bacteria. Commensal bacteria have begun to receive much attention in recent years, especially in the gut where there is growing evidence of complex interactions with the adaptive immune system. In the present study, we observed that commensal skin bacteria are recognized by major populations of T cells in skin-draining lymph nodes of mice. Recombination activating gene 1 (Rag1)(-/-) mice, which lack adaptive immune cells, contained living skin-derived bacteria and bacterial sequences, especially mycobacteria, in their skin-draining lymph nodes. T cells from skin-draining lymph nodes of normal mice were shown, in vitro, to specifically recognize bacteria of several species that were grown from Rag1(-/-) lymph nodes. T cells from skin-draining lymph nodes, transferred into Rag1(-/-) mice proliferated in skin-draining lymph nodes, expressed a restricted T-cell receptor spectrotype and produced cytokines. Transfer of T cells into Rag1(-/-) mice had the effect of reducing bacterial sequences in skin-draining lymph nodes and in skin itself. Antibacterial effects of transferred T cells were dependent on IFNγ and IL-17A. These studies suggest a previously unrecognized role for T cells in controlling skin commensal bacteria and provide a mechanism to account for cutaneous infections and mycobacterial infections in T-cell-deficient patients.

摘要

适应性免疫系统为抵御病原性细菌提供了关键防御。近年来,共生细菌开始受到广泛关注,尤其是在肠道中,越来越多的证据表明它们与适应性免疫系统之间存在着复杂的相互作用。在本研究中,我们观察到,共生皮肤细菌被小鼠皮肤引流淋巴结中的主要 T 细胞群体所识别。缺乏适应性免疫细胞的重组激活基因 1(Rag1)(-/-)小鼠的皮肤引流淋巴结中存在存活的皮肤来源细菌和细菌序列,尤其是分枝杆菌。从正常小鼠皮肤引流淋巴结中分离出的 T 细胞在体外可特异性识别从 Rag1(-/-)淋巴结中培养出的几种细菌。从皮肤引流淋巴结转移而来的 T 细胞在 Rag1(-/-)小鼠的皮肤引流淋巴结中增殖,表达受限的 T 细胞受体谱型并产生细胞因子。将 T 细胞转移到 Rag1(-/-)小鼠中,可减少皮肤引流淋巴结和皮肤本身中的细菌序列。转移的 T 细胞的抗菌作用依赖于 IFNγ 和 IL-17A。这些研究表明 T 细胞在控制皮肤共生细菌方面发挥了先前未被认识的作用,并为 T 细胞缺陷患者的皮肤感染和分枝杆菌感染提供了一种解释机制。

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