Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11548-53. doi: 10.1073/pnas.1108924108. Epub 2011 Jun 27.
Vertebrates typically harbor a rich gastrointestinal microbiota, which has coevolved with the host over millennia and is essential for several host physiological functions, in particular maturation of the immune system. Recent studies have highlighted the importance of a single bacterial species, segmented filamentous bacteria (SFB), in inducing a robust T-helper cell type 17 (Th17) population in the small-intestinal lamina propria (SI-LP) of the mouse gut. Consequently, SFB can promote IL-17-dependent immune and autoimmune responses, gut-associated as well as systemic, including inflammatory arthritis and experimental autoimmune encephalomyelitis. Here, we exploit the incomplete penetrance of SFB colonization of NOD mice in our animal facility to explore its impact on the incidence and course of type 1 diabetes in this prototypical, spontaneous model. There was a strong cosegregation of SFB positivity and diabetes protection in females, but not in males, which remained relatively disease-free regardless of the SFB status. In contrast, insulitis did not depend on SFB colonization. SFB-positive, but not SFB-negative, females had a substantial population of Th17 cells in the SI-LP, which was the only significant, repeatable difference in the examined T-cell compartments of the gut, pancreas, or systemic lymphoid tissues. Th17-signature transcripts dominated the very limited SFB-induced molecular changes detected in SI-LP CD4(+) T cells. Thus, a single bacterium, and the gut immune system alterations associated with it, can either promote or protect from autoimmunity in predisposed mouse models, probably reflecting their variable dependence on different Th subsets.
脊椎动物通常拥有丰富的胃肠道微生物群，这些微生物与宿主在数千年中共同进化，对宿主的几种生理功能至关重要，尤其是免疫系统的成熟。最近的研究强调了一种单一细菌物种，即分段丝状菌（SFB），在诱导小鼠肠道小肠固有层（SI-LP）中产生强大的辅助性 T 细胞 17（Th17）群体中的重要性。因此，SFB 可以促进依赖于 IL-17 的免疫和自身免疫反应，包括肠道相关和系统性炎症性关节炎和实验性自身免疫性脑脊髓炎。在这里，我们利用我们的动物设施中 NOD 小鼠中 SFB 定植的不完全穿透性来探索其对这种典型自发性模型中 1 型糖尿病的发病率和病程的影响。在女性中，SFB 阳性与糖尿病保护之间存在强烈的共分离，但在男性中则没有，无论 SFB 状态如何，男性都相对没有患病。相比之下，胰岛炎不依赖于 SFB 定植。SFB 阳性但 SFB 阴性的女性在 SI-LP 中有大量的 Th17 细胞，这是在检查的肠道、胰腺或系统淋巴组织的 T 细胞区室中唯一的显著、可重复的差异。Th17 特征转录物主导了在 SI-LP CD4（+）T 细胞中检测到的非常有限的 SFB 诱导的分子变化。因此，一种单一的细菌，以及与之相关的肠道免疫系统改变，可以促进或保护易患自身免疫的小鼠模型免受自身免疫，这可能反映了它们对不同 Th 亚群的不同依赖。
