Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris, France.
mBio. 2013 Dec 10;4(6):e00707-13. doi: 10.1128/mBio.00707-13.
The intestinal tract is the largest reservoir of microbes in the human body. The intestinal microbiota is thought to be able to modulate alterations of the gut induced by enteropathogens, thereby maintaining homeostasis. Listeria monocytogenes is the agent of listeriosis, an infection transmitted to humans upon ingestion of contaminated food. Crossing of the intestinal barrier is a critical step of the infection before dissemination into deeper organs. Here, we investigated the role of the intestinal microbiota in the regulation of host protein-coding genes and microRNA (miRNA or miR) expression during Listeria infection. We first established the intestinal miRNA signatures corresponding to the 10 most highly expressed miRNAs in the murine ileum of conventional and germfree mice, noninfected and infected with Listeria. Next, we identified 6 miRNAs whose expression decreased upon Listeria infection in conventional mice. Strikingly, five of these miRNA expression variations (in miR-143, miR-148a, miR-200b, miR-200c, and miR-378) were dependent on the presence of the microbiota. In addition, as is already known, protein-coding genes were highly affected by infection in both conventional and germfree mice. By crossing bioinformatically the predicted targets of the miRNAs to our whole-genome transcriptomic data, we revealed an miRNA-mRNA network that suggested miRNA-mediated global regulation during intestinal infection. Other recent studies have revealed an miRNA response to either bacterial pathogens or commensal bacteria. In contrast, our work provides an unprecedented insight into the impact of the intestinal microbiota on host transcriptional reprogramming during infection by a human pathogen.
While the crucial role of miRNAs in regulating the host response to bacterial infection is increasingly recognized, the involvement of the intestinal microbiota in the regulation of miRNA expression has not been explored in detail. Here, we investigated the impact of the intestinal microbiota on the regulation of protein-coding genes and miRNA expression in a host infected by L. monocytogenes, a food-borne pathogen. We show that the microbiota interferes with the microRNA response upon oral Listeria infection and identify several protein-coding target genes whose expression correlates inversely with that of the miRNA. Further investigations of the regulatory networks involving miR-143, miR-148a, miR-200b, miR-200c, and miR-378 will provide new insights into the impact of the intestinal microbiota on the host upon bacterial infection.
肠道是人体内最大的微生物储存库。肠道微生物群被认为能够调节肠道病原体引起的肠道改变，从而维持体内平衡。单核细胞增生李斯特菌是李斯特菌病的病原体，这种感染是通过摄入受污染的食物传播给人类的。穿过肠道屏障是感染向更深层器官传播之前的关键步骤。在这里，我们研究了肠道微生物群在调节宿主蛋白编码基因和微 RNA（miRNA 或 miR）表达方面的作用，即在李斯特菌感染期间。我们首先建立了常规和无菌小鼠回肠中 10 个表达最高的 miRNA 对应的肠道 miRNA 特征，这些小鼠未感染和感染李斯特菌。接下来，我们确定了 6 个在常规小鼠李斯特菌感染后表达降低的 miRNA。引人注目的是，这 5 个 miRNA 表达变化（miR-143、miR-148a、miR-200b、miR-200c 和 miR-378）依赖于微生物群的存在。此外，正如已经知道的，感染在常规和无菌小鼠中都会强烈影响蛋白质编码基因。通过将 miRNA 的预测靶标与我们的全基因组转录组数据进行生物信息学交叉，我们揭示了一个 miRNA-mRNA 网络，表明 miRNA 在肠道感染期间对全局进行了调节。其他最近的研究揭示了 miRNA 对细菌病原体或共生菌的反应。相比之下，我们的工作提供了一个前所未有的见解，即肠道微生物群在人类病原体感染期间对宿主转录重编程的影响。
虽然 miRNA 在调节宿主对细菌感染的反应中的关键作用越来越受到重视，但肠道微生物群在 miRNA 表达调节中的作用尚未得到详细探讨。在这里，我们研究了肠道微生物群在李斯特菌感染宿主时对蛋白质编码基因和 miRNA 表达的调节作用，李斯特菌是一种食源性病原体。我们表明，微生物群会干扰口服李斯特菌感染时的 microRNA 反应，并确定了几个表达与 miRNA 表达呈负相关的蛋白质编码靶基因。对涉及 miR-143、miR-148a、miR-200b、miR-200c 和 miR-378 的调控网络的进一步研究将为肠道微生物群对细菌感染时宿主的影响提供新的见解。
