Immunity：天然肠道微生物菌群可增强机体免疫力

来自天然肠道细菌的信号对于机体免疫效应对抗病毒和细菌来说非常有效，这项研究成果由弗莱堡大学的研究者完成，刊登在了近日的国际杂志Immunity上。

数以万亿计的细菌生存在健康人群以及其它动物的肠道中，这种天然的肠道细菌对于维持机体消化和维生素代谢以及对于宿主的健康功不可没。近日，研究者通过研究指出肠道微生物菌群在肠道免疫系统的形成上扮演着重要作用，如果改变肠道菌群的组成将会增加食品过敏或者肠道炎性疾病的风险。以前我们并不清楚扩大肠道菌群的广度可以影响肠道外部的免疫过程，比如抵御病毒的能力等等。

研究者用不同的过滤性病毒感染了两组小鼠，两组小鼠中一组有正常的肠道菌群，另外一组仅仅是所谓的无菌小鼠。相比正常小鼠来说，无菌小鼠的免疫效应会大幅降低，并且产生严重的疾病，当研究者给予无菌小鼠正常小鼠的体内肠道微生物菌群时，其免疫效应便可以恢复。

Diefenbach的研究小组在分子水平上成功地定位了无菌小鼠的缺陷，这些小鼠并不能产生可溶解的炎症介质，比如所谓的I型干扰素等。来自天然免疫系统的树突状细胞可以通过产生介质对感染快速应答，如果其不存在的话，机体将不能针对细菌产生足够的免疫防御力，研究者揭示了来自肠道细菌的信号可以提供树突状细胞产生的条件，这种条件依赖于细胞核中DNA的水平，并且使得基因编码更多的可溶解性介质来进行识别。研究者表示，这是首次揭示由于抗生素、卫生和生活方式的改变导致天然肠道菌群的改变，进而将影响机体整体的免疫系统。

编译自：Natural Intestinal Flora Strengthen Immune System

doi:10.1016/j.immuni.2012.05.020
PMC:
PMID:

Priming of Natural Killer Cells by Nonmucosal Mononuclear Phagocytes Requires Instructive Signals from Commensal Microbiota

Stephanie C. Ganal Stephanie L. Sanos Carsten Kallfass Karin Oberle Caroline Johner Carsten Kirschning Stefan Lienenklaus Siegfried Weiss Peter Staeheli Peter Aichele Andreas Diefenbach

Mononuclear phagocytes are an important component of an innate immune system perceived as a system ready to react upon encounter of pathogens. Here, we show that in response to microbial stimulation, mononuclear phagocytes residing in nonmucosal lymphoid organs of germ-free mice failed to induce expression of a set of inflammatory response genes, including those encoding the various type I interferons (IFN-I). Consequently, NK cell priming and antiviral immunity were severely compromised. Whereas pattern recognition receptor signaling and nuclear translocation of the transcription factors NF-B and IRF3 were normal in mononuclear phagocytes of germ-free mice, binding to their respective cytokine promoters was impaired, which correlated with the absence of activating histone marks. Our data reveal a previously unrecognized role for postnatally colonizing microbiota in the introduction of chromatin level changes in the mononuclear phagocyte system, thereby poising expression of central inflammatory genes to initiate a powerful systemic immune response during viral infection.