Polymorphic Immune Mechanisms Regulate Commensal Repertoire
Polymorphic Immune Mechanisms Regulate Commensal Repertoire
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DOI：
10.1016/j.celrep.2019.09.010
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发表时间：
2019-10-15
期刊：
影响因子：
8.8
通讯作者：
Chervonsky, Alexander
中科院分区：
文献类型：
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作者：
Khan, Aly A.;Yurkovetskiy, Leonid;Chervonsky, Alexander
环境影响（感染和饮食）强烈影响宿主的微生物群。然而，宿主遗传学可能会影响肠道菌群，同卵双胞胎的微生物组与异卵双胞胎相比具有更大的相似性。人类基因组和微生物组的变异性使得对调节肠道菌群的多态性机制的理解变得复杂。虽然动物研究允许基因修改，但它们对被称为“笼子”或“遗产”效应的影响很敏感。在这里，我们分析了各种遗传背景的无外胚小鼠，包括免疫缺陷和主要组织相容性复合体（MHC）同源株，接受相同的输入微生物群。宿主的多态性机制影响肠道微生物组，并且先天性（抗微生物肽、补体、正五肽和影响微生物存活的酶）和适应性（MHC依赖性和MHC非依赖性）途径都影响微生物群。在我们的实验中，多态性机制仅调节有限数量的微生物谱系（与其丰度无关）。我们的比较分析表明，一些微生物可能受益于它们引起的特异性免疫反应。
Environmental influences (infections and diet) strongly affect a host's microbiota. However, host genetics may influence commensal communities, as suggested by the greater similarity between the microbiomes of identical twins compared to nonidentical twins. Variability of human genomes and microbiomes complicates the understanding of polymorphic mechanisms regulating the commensal communities. Whereas animal studies allow genetic modifications, they are sensitive to influences known as "cage" or "legacy" effects. Here, we analyze exgerm-free mice of various genetic backgrounds, including immunodeficient and major histocompatibility complex (MHC) congenic strains, receiving identical input microbiota. The host's polymorphic mechanisms affect the gut microbiome, and both innate (anti-microbial peptides, complement, pentraxins, and enzymes affecting microbial survival) and adaptive (MHC-dependent and MHC-independent) pathways influence the microbiota. In our experiments, polymorphic mechanisms regulate only a limited number of microbial lineages (independently of their abundance). Our comparative analyses suggest that some microbes may benefit from the specific immune responses that they elicit.