Innate immune responses to gut microbiota differ between oceanic and freshwater threespine stickleback populations.
Innate immune responses to gut microbiota differ between oceanic and freshwater threespine stickleback populations.
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DOI：
10.1242/dmm.021881
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发表时间：
2016-02
影响因子：
4.3
通讯作者：
Guillemin K
中科院分区：
文献类型：
--
作者：
Milligan-Myhre K;Small CM;Mittge EK;Agarwal M;Currey M;Cresko WA;Guillemin K
动物宿主必须与有益微生物共存，同时能够对病原微生物产生快速的、非特异性的先天免疫反应。这种平衡是如何实现的还不完全清楚，这种关系的破坏可能导致疾病。对驻留微生物的过度炎症反应是某些胃肠道病变如炎症性肠病（IBD）的特征。IBD的免疫失调具有复杂的遗传基础，不能用单基因敲除模型完全概括。要更深入地了解对常驻微生物的先天免疫反应的遗传调控，需要能够使用具有复杂遗传变异的脊椎动物模型在存在和不存在微生物群的情况下测量免疫反应。在这里，我们描述了一种新的gnotobiotic脊椎动物模型，以探索自然的遗传变异，有助于对微生物群的先天免疫反应的差异。三棘鱼Gasterosteus aculeatus是一种从海洋鱼类向淡水鱼类重复进化的鱼类，其复杂性状的发育遗传学研究一直是一个热点。我们建立了饲养无菌棘鱼幼虫和与单一细菌分离物单相关的无菌动物的方法。我们的特点是这些鱼的先天免疫反应居民肠道微生物通过定量中性粒细胞在常规饲养的monoassociated或无菌刺鱼从海洋和淡水种群生长在一个共同的中间盐度环境。我们发现，野生和实验室中的海洋和淡水鱼共享许多肠道微生物群落成员。然而，海洋鱼类对住宅微生物群产生强烈的免疫反应，而淡水鱼类通常不会。一个强大的先天免疫反应，统一观察到海洋家庭，但这种反应不同的淡水鱼家庭。因此，我们开发的gnotobiotic棘鱼模型为未来的研究提供了一个平台，以绘制对微生物免疫反应变化的自然遗传基础。总结：我们开发了一种知菌三刺鱼系统，以确定微生物群炎症反应变异的细胞和遗传基础。
Animal hosts must co-exist with beneficial microbes while simultaneously being able to mount rapid, non-specific, innate immune responses to pathogenic microbes. How this balance is achieved is not fully understood, and disruption of this relationship can lead to disease. Excessive inflammatory responses to resident microbes are characteristic of certain gastrointestinal pathologies such as inflammatory bowel disease (IBD). The immune dysregulation of IBD has complex genetic underpinnings that cannot be fully recapitulated with single-gene-knockout models. A deeper understanding of the genetic regulation of innate immune responses to resident microbes requires the ability to measure immune responses in the presence and absence of the microbiota using vertebrate models with complex genetic variation. Here, we describe a new gnotobiotic vertebrate model to explore the natural genetic variation that contributes to differences in innate immune responses to microbiota. Threespine stickleback, Gasterosteus aculeatus, has been used to study the developmental genetics of complex traits during the repeated evolution from ancestral oceanic to derived freshwater forms. We established methods to rear germ-free stickleback larvae and gnotobiotic animals monoassociated with single bacterial isolates. We characterized the innate immune response of these fish to resident gut microbes by quantifying the neutrophil cells in conventionally reared monoassociated or germ-free stickleback from both oceanic and freshwater populations grown in a common intermediate salinity environment. We found that oceanic and freshwater fish in the wild and in the laboratory share many intestinal microbial community members. However, oceanic fish mount a strong immune response to residential microbiota, whereas freshwater fish frequently do not. A strong innate immune response was uniformly observed across oceanic families, but this response varied among families of freshwater fish. The gnotobiotic stickleback model that we have developed therefore provides a platform for future studies mapping the natural genetic basis of the variation in immune response to microbes. Summary: We developed a gnotobiotic threespine stickleback system to identify the cellular and genetic bases for variation in inflammatory responses to microbiota.