College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi Province, 030801, China.
State Key Laboratory of Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, 730000, China.
NPJ Biofilms Microbiomes. 2023 Jun 24;9(1):43. doi: 10.1038/s41522-023-00410-7.
Tissue-dwelling helminths affect billions of people around the world. They are potent manipulators of the host immune system, prominently by promoting regulatory T cells (Tregs) and are generally associated with a modified host gut microbiome. However, the role of the gut microbiota in the immunomodulatory processes for these non-intestinal parasites is still unclear. In the present study, we used an extra-intestinal cestode helminth model-larval Echinococcus multilocularis to explore the tripartite partnership (host-helminth-bacteria) in the context of regulating colonic Tregs in Balb/c mice. We showed that larval E. multilocularis infection in the peritoneal cavity attenuated colitis in Balb/c mice and induced a significant expansion of colonic Foxp3 Treg populations. Fecal microbiota depletion and transplantation experiments showed that the gut microbiota contributed to increasing Tregs after the helminth infection. Shotgun metagenomic and metabolic analyses revealed that the gut microbiome structure after infection was significantly shifted with a remarkable increase of Lactobacillus reuteri and that the microbial metabolic capability was reprogrammed to produce more Treg cell regulator-short-chain fatty acids in feces. Furthermore, we also prove that the L. reuteri strain elevated in infected mice was sufficient to promote the colonic Treg frequency and its growth was potentially associated with T cell-dependent immunity in larval E. multilocularis infection. Collectively, these findings indicate that the extraintestinal helminth drives expansions of host colonic Tregs through the gut microbes. This study suggests that the gut microbiome serves as a critical component of anti-inflammation effects even for a therapy based on an extraintestinal helminth.
组织内寄生虫影响着全球数十亿人。它们是宿主免疫系统的有力调控者，主要通过促进调节性 T 细胞（Tregs）来实现，并与宿主肠道微生物组的改变有关。然而，肠道微生物群在这些非肠道寄生虫的免疫调节过程中的作用尚不清楚。在本研究中，我们使用一种肠外绦虫寄生虫模型——幼虫细粒棘球蚴，来探索在调节 Balb/c 小鼠结肠 Tregs 时，宿主-寄生虫-细菌三方伙伴关系。我们发现，幼虫细粒棘球蚴在腹腔内的感染减轻了 Balb/c 小鼠的结肠炎，并显著增加了结肠 Foxp3+ Treg 群体。粪便微生物群耗竭和移植实验表明，在寄生虫感染后，肠道微生物群有助于增加 Tregs。 shotgun 宏基因组和代谢分析显示，感染后肠道微生物组结构发生了显著变化，乳杆菌属 reuteri 的数量显著增加，微生物代谢能力被重新编程，以在粪便中产生更多的 Treg 细胞调节剂——短链脂肪酸。此外，我们还证明，在感染小鼠中升高的 reuteri 菌株足以促进结肠 Treg 频率的增加，其生长可能与幼虫细粒棘球蚴感染中的 T 细胞依赖性免疫有关。总之，这些发现表明，肠外寄生虫通过肠道微生物群促进宿主结肠 Tregs 的扩增。本研究表明，肠道微生物群甚至是一种基于肠外寄生虫的治疗方法的抗炎作用的关键组成部分。
