Rapid environmental effects on gut nematode susceptibility in rewilded mice
Rapid environmental effects on gut nematode susceptibility in rewilded mice
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DOI：
10.1371/journal.pbio.2004108
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发表时间：
2018-03-01
期刊：
影响因子：
9.8
通讯作者：
Graham, Andrea L.
中科院分区：
文献类型：
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作者：
Leung, Jacqueline M.;Budischak, Sarah A.;Graham, Andrea L.
遗传和环境因素影响宿主对感染的易感性，但环境变化如何以及多快地改变哺乳动物基因型的易感性仍然未知。本文研究了半自然环境对近交系C57BL/6小鼠线虫敏感性的影响。我们假设自然暴露于微生物可能直接（例如，通过营养相互作用）或间接（例如，通过微生物诱导的免疫反应）改变室外饲养的小鼠体内线虫的孵化、生长和存活。我们发现，虽然C57BL/6小鼠在清洁的实验室条件下对高剂量的线虫（Trichuris muris）卵具有抗性，但暴露于室外环境显著增加了它们对感染的易感性，这可以通过增加蠕虫负担和蠕虫生物量来证明。事实上，在户外饲养的小鼠体内的蠕虫数量与信号换能器和转录激活因子（STATE）敲除小鼠一样多，后者在清除线虫所必需的2型免疫反应中存在遗传缺陷。利用粪便样本的16S核糖体RNA测序，我们发现户外小鼠的微生物多样性和特异性细菌分类群增强，可预测线虫负荷。我们还观察到，居住在户外的感染小鼠固有层和肠系膜淋巴结（MLN）细胞的2型免疫反应减少，1型免疫反应增加。重要的是，在我们的实验设计中，不同组的老鼠在户外活动之前或之后接受了线虫卵。这种对比时间的重新野生化表明，蠕虫的孵化增强并不足以解释蠕虫负担的增加；相反，正如假设的那样，微生物增强和蠕虫生长和生存的1型免疫促进也是解释我们的结果所必需的。这些发现表明，环境可以迅速而显著地塑造肠道微生物群落和粘膜对线虫感染的反应，从而导致基因相似的宿主之间寄生虫排出率的差异。
Genetic and environmental factors shape host susceptibility to infection, but how and how rapidly environmental variation might alter the susceptibility of mammalian genotypes remains unknown. Here, we investigate the impacts of seminatural environments upon the nematode susceptibility profiles of inbred C57BL/6 mice. We hypothesized that natural exposure to microbes might directly (e.g., via trophic interactions) or indirectly (e.g., via microbe-induced immune responses) alter the hatching, growth, and survival of nematodes in mice housed outdoors. We found that while C57BL/6 mice are resistant to high doses of nematode (Trichuris muris) eggs under clean laboratory conditions, exposure to outdoor environments significantly increased their susceptibility to infection, as evidenced by increased worm burdens and worm biomass. Indeed, mice kept outdoors harbored as many worms as signal transducer and activator of transcription 6 (STATE) knockout mice, which are genetically deficient in the type 2 immune response essential for clearing nematodes. Using 16S ribosomal RNA sequencing of fecal samples, we discovered enhanced microbial diversity and specific bacterial taxa predictive of nematode burden in outdoor mice. We also observed decreased type 2 and increased type 1 immune responses in lamina propria and mesenteric lymph node (MLN) cells from infected mice residing outdoors. Importantly, in our experimental design, different groups of mice received nematode eggs either before or after moving outdoors. This contrasting timing of rewilding revealed that enhanced hatching of worms was not sufficient to explain the increased worm burdens; instead, microbial enhancement and type 1 immune facilitation of worm growth and survival, as hypothesized, were also necessary to explain our results. These findings demonstrate that environment can rapidly and significantly shape gut microbial communities and mucosal responses to nematode infections, leading to variation in parasite expulsion rates among genetically similar hosts.