Department of Veterinary Medicine, Institute of Immunology, Freie Universität Berlin, Berlin, Germany.
Bioinformatics Unit (MF 1), Robert Koch Institute, Berlin, Germany.
Front Immunol. 2018 Oct 8;9:2282. doi: 10.3389/fimmu.2018.02282. eCollection 2018.
Intestinal parasitic nematodes live in intimate contact with the host microbiota. Changes in the microbiome composition during nematode infection affect immune control of the parasites and shifts in the abundance of bacterial groups have been linked to the immunoregulatory potential of nematodes. Here we asked if the small intestinal parasite produces factors with antimicrobial activity, senses its microbial environment and if the anti-nematode immune and regulatory responses are altered in mice devoid of gut microbes. We found that excretory/secretory products exhibited antimicrobial activity against gram bacteria. Parasites from germ-free mice displayed alterations in gene expression, comprising factors with putative antimicrobial functions such as chitinase and lysozyme. Infected germ-free mice developed increased small intestinal Th2 responses coinciding with a reduction in local Foxp3RORγt regulatory T cells and decreased parasite fecundity. Our data suggest that nematodes sense their microbial surrounding and have evolved factors that limit the outgrowth of certain microbes. Moreover, the parasites benefit from microbiota-driven immune regulatory circuits, as an increased ratio of intestinal Th2 effector to regulatory T cells coincides with reduced parasite fitness in germ-free mice.
肠道寄生线虫与宿主微生物群密切接触。线虫感染过程中微生物组组成的变化影响对寄生虫的免疫控制，细菌群丰度的变化与线虫的免疫调节潜能有关。在这里，我们想知道这种小肠寄生虫是否会产生具有抗菌活性的因子，是否能感知其微生物环境，以及缺乏肠道微生物的小鼠的抗线虫免疫和调节反应是否会发生改变。我们发现，排泄物/分泌物对革兰氏阳性菌具有抗菌活性。来自无菌小鼠的寄生虫表现出基因表达的改变，包括具有潜在抗菌功能的因子，如几丁质酶和溶菌酶。感染无菌小鼠的小肠 Th2 反应增加，同时局部 Foxp3RORγt 调节性 T 细胞减少，寄生虫丰度降低。我们的数据表明，线虫感知其微生物环境，并进化出限制某些微生物生长的因子。此外，寄生虫受益于微生物驱动的免疫调节回路，因为增加肠道 Th2 效应物与调节性 T 细胞的比例与无菌小鼠中寄生虫适应性降低相吻合。
