The Immune and Non-Immune Pathways That Drive Chronic Gastrointestinal Helminth Burdens in the Wild.
The Immune and Non-Immune Pathways That Drive Chronic Gastrointestinal Helminth Burdens in the Wild.
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DOI：
10.3389/fimmu.2018.00056
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发表时间：
2018
影响因子：
7.3
通讯作者：
Pedersen AB
中科院分区：
文献类型：
--
作者：
Babayan SA;Liu W;Hamilton G;Kilbride E;Rynkiewicz EC;Clerc M;Pedersen AB
寄生蠕虫在维持慢性感染负担的能力方面非常有弹性，尽管（或者可能是因为）它们的宿主的免疫反应。解释寄生虫如何维持这些终身感染，确定调节蠕虫感染负担的保护性免疫机制，并设计对抗蠕虫感染的药物和治疗方法，同时保护宿主健康，需要更好地了解免疫系统在自然栖息地中的功能。因此，有必要补充机制的实验室为基础的研究与野生种群及其自然寄生虫群落的研究。不幸的是，非模式物种的免疫学工具的相对缺乏阻碍了这些类型的研究。值得庆幸的是，高通量组学平台的最新进展为免疫学家提供了强大且日益实用的手段，使其超越了传统的基于实验室的模型生物。然而，将代谢和免疫功能分配给新物种中的基因、转录本和蛋白质，并评估它们如何与其他生理和环境因素相互作用，需要确定它们的表达和感染之间的定量关系。在这里，我们使用有监督的机器学习来识别与胃肠道线虫Heligmosomoides polygyrus在其天然宿主--野生林鼠Apodemus sylvaticus中的负担密切相关的基因网络。在跨越两个野生种群和两个不同季节的34只小鼠中，我们发现了17，639个转录本聚集在131个加权基因网络中。这些聚类强有力地预测了H。多脑回的负担，包括众所周知的效应和调节免疫基因，但也揭示了一些基因与组织的稳态和造血功能的维持，迄今为止很少受到关注。然后，我们测试了通过药物治疗实验性地减少蠕虫负担对那些脓毒症保护性免疫因子的影响。尽管H.在多脑回蠕虫中，治疗对基因表达的影响令人惊讶地小。两者合计，这些结果表明，主机平衡组织稳态和保护性免疫，导致相对稳定的免疫，因此，寄生虫学的配置文件。在未来，将我们的方法应用于来自其他人群的大量样本将有助于进一步提高我们检测决定野外慢性胃肠道蠕虫负担的免疫途径的能力。
Parasitic helminths are extremely resilient in their ability to maintain chronic infection burdens despite (or maybe because of) their hosts’ immune response. Explaining how parasites maintain these lifelong infections, identifying the protective immune mechanisms that regulate helminth infection burdens, and designing prophylactics and therapeutics that combat helminth infection, while preserving host health requires a far better understanding of how the immune system functions in natural habitats than we have at present. It is, therefore, necessary to complement mechanistic laboratory-based studies with studies on wild populations and their natural parasite communities. Unfortunately, the relative paucity of immunological tools for non-model species has held these types of studies back. Thankfully, recent progress in high-throughput ‘omics platforms provide powerful and increasingly practical means for immunologists to move beyond traditional lab-based model organisms. Yet, assigning both metabolic and immune function to genes, transcripts, and proteins in novel species and assessing how they interact with other physiological and environmental factors requires identifying quantitative relationships between their expression and infection. Here, we used supervised machine learning to identify gene networks robustly associated with burdens of the gastrointestinal nematode Heligmosomoides polygyrus in its natural host, the wild wood mice Apodemus sylvaticus. Across 34 mice spanning two wild populations and across two different seasons, we found 17,639 transcripts that clustered in 131 weighted gene networks. These clusters robustly predicted H. polygyrus burden and included well-known effector and regulatory immune genes, but also revealed a number of genes associated with the maintenance of tissue homeostasis and hematopoiesis that have so far received little attention. We then tested the effect of experimentally reducing helminth burdens through drug treatment on those putatively protective immune factors. Despite the near elimination of H. polygyrus worms, the treatment had surprisingly little effect on gene expression. Taken together, these results suggest that hosts balance tissue homeostasis and protective immunity, resulting in relatively stable immune and, consequently, parasitological profiles. In the future, applying our approach to larger numbers of samples from additional populations will help further increase our ability to detect the immune pathways that determine chronic gastrointestinal helminth burdens in the wild.
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DOI：
10.4049/jimmunol.181.4.2414
发表时间：
2008-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Elliott DE;Metwali A;Leung J;Setiawan T;Blum AM;Ince MN;Bazzone LE;Stadecker MJ;Urban JF Jr;Weinstock JV
通讯作者：
Weinstock JV
影响因子：
4
作者：
Ferrari, N.;Rosa, R.;Hudson, P. J.
通讯作者：
Hudson, P. J.
影响因子：
4.9
作者：
Friberg, I. M.;Little, S.;Bradley, J. E.
通讯作者：
Bradley, J. E.
影响因子：
16.6
作者：
Abolins S;King EC;Lazarou L;Weldon L;Hughes L;Drescher P;Raynes JG;Hafalla JCR;Viney ME;Riley EM
通讯作者：
Riley EM
影响因子：
2.4
作者：
Behnke, J. M.;Eira, C.;Lewis, J. W.
通讯作者：
Lewis, J. W.