Data from: Rapid environmental effects on gut nematode susceptibility in rewilded mice

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 (STAT6) 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.

遗传与环境因素共同塑造宿主对感染的易感性，但环境变化如何、以多快的速度改变哺乳动物基因型的易感性，目前仍未明确。本研究探究了半自然环境对近交系C57BL/6小鼠线虫易感性特征的影响。我们提出假说：自然暴露于微生物环境，可通过直接途径（例如通过营养相互作用）或间接途径（例如通过微生物诱导的免疫应答），改变户外饲养小鼠体内线虫的孵化、生长与存活情况。研究发现，尽管在洁净的实验室条件下，C57BL/6小鼠对高剂量的鼠鞭虫（Trichuris muris）虫卵具有抗性，但暴露于户外环境后，其感染易感性显著升高，这一点可通过虫荷增加与虫体生物量上升得到证实。事实上，户外饲养的小鼠体内寄生的线虫数量与信号转导与转录激活因子6（signal transducer and activator of transcription 6, STAT6）基因敲除小鼠相当——这类小鼠存在清除线虫所必需的2型免疫应答的遗传缺陷。通过对粪便样本进行16S核糖体RNA（16S ribosomal RNA）测序，我们发现户外小鼠的肠道微生物多样性更高，且存在可预测线虫荷量的特异性细菌类群。我们还观察到，户外感染小鼠的固有层与肠系膜淋巴结（mesenteric lymph node, MLN）细胞中，2型免疫应答水平降低、1型免疫应答水平升高。重要的是，在本实验设计中，不同组小鼠分别在转移至户外环境之前或之后接受线虫虫卵接种。这种差异化的野外暴露时序揭示：线虫孵化率提升不足以解释虫荷的增加；正如假说所提出的，微生物群落优化与1型免疫对蠕虫生长与存活的促进作用，同样是解释本研究结果的必要条件。上述研究结果表明，环境可快速且显著地塑造肠道微生物群落与黏膜针对线虫感染的免疫应答，进而导致遗传背景相似的宿主之间寄生虫排出率产生差异。