Rewilding Nod2 and Atg16l1 Mutant Mice Uncovers Genetic and Environmental Contributions to Microbial Responses and Immune Cell Composition.,Cell Host & Microbe

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Rewilding Nod2 and Atg16l1 Mutant Mice Uncovers Genetic and Environmental Contributions to Microbial Responses and Immune Cell Composition.
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2020-03-24 , DOI: 10.1016/j.chom.2020.03.001
Jian-Da Lin ₁ , Joseph C Devlin ₂ , Frank Yeung ₃ , Caroline McCauley ₄ , Jacqueline M Leung ₅ , Ying-Han Chen ₆ , Alex Cronkite ₇ , Christina Hansen ₅ , Charlotte Drake-Dunn ₆ , Kelly V Ruggles ₈ , Ken Cadwell ₉ , Andrea L Graham ₅ , P'ng Loke ₁

Affiliation

Department of Microbiology, NYU Grossman School of Medicine, New York University School of Medicine, New York, NY 10016, USA; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Department of Microbiology, NYU Grossman School of Medicine, New York University School of Medicine, New York, NY 10016, USA; Sackler Institute of Graduate Biomedical Sciences, NYU Grossman School of Medicine, New York University, New York, NY 10016, USA; Institute of Systems Genetics, NYU Grossman School of Medicine, New York University School of Medicine, New York, NY 10016, USA.
Sackler Institute of Graduate Biomedical Sciences, NYU Grossman School of Medicine, New York University, New York, NY 10016, USA; Kimmel Center for Biology and Medicine at the Skirball Institute, NYU Grossman School of Medicine, New York University School of Medicine, New York, NY 10016, USA.
Department of Microbiology, NYU Grossman School of Medicine, New York University School of Medicine, New York, NY 10016, USA.
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA.
Kimmel Center for Biology and Medicine at the Skirball Institute, NYU Grossman School of Medicine, New York University School of Medicine, New York, NY 10016, USA.
Department of Microbiology, NYU Grossman School of Medicine, New York University School of Medicine, New York, NY 10016, USA; Kimmel Center for Biology and Medicine at the Skirball Institute, NYU Grossman School of Medicine, New York University School of Medicine, New York, NY 10016, USA.
Division of Translational Medicine, Department of Medicine, NYU Grossman School of Medicine, New York University School of Medicine, New York, NY 10016, USA; Institute of Systems Genetics, NYU Grossman School of Medicine, New York University School of Medicine, New York, NY 10016, USA.
Department of Microbiology, NYU Grossman School of Medicine, New York University School of Medicine, New York, NY 10016, USA; Kimmel Center for Biology and Medicine at the Skirball Institute, NYU Grossman School of Medicine, New York University School of Medicine, New York, NY 10016, USA; Division of Gastroenterology and Hepatology, Department of Medicine, New York University Langone Health, New York, NY 10016, USA.

The relative contributions of genetic and environmental factors to variation in immune responses are poorly understood. Here, we performed a phenotypic analysis of immunological parameters in laboratory mice carrying susceptibility genes implicated in inflammatory bowel disease (IBD) (Nod2 and Atg16l1) upon exposure to environmental microbes. Mice were released into an outdoor enclosure (rewilded) and then profiled for immune responses in the blood and lymph nodes. Variations of immune cell populations were largely driven by the environment, whereas cytokine production elicited by microbial antigens was more affected by the genetic mutations. We identified transcriptional signatures in the lymph nodes associated with differences in T cell populations. Subnetworks associated with responses against Clostridium perfringens, Candida albicans, and Bacteroides vulgatus were also coupled with rewilding. Therefore, exposing laboratory mice with genetic mutations to a natural environment uncovers different contributions to variations in microbial responses and immune cell composition.

中文翻译：

野蛮的Nod2和Atg16l1突变小鼠揭示了微生物反应和免疫细胞组成的遗传和环境贡献。

遗传和环境因素对免疫应答变化的相对贡献了解甚少。在这里，我们进行了实验小鼠的免疫学参数的表型分析，这些小鼠携带与环境性微生物接触后与炎症性肠病（IBD）（Nod2和Atg16l1）有关的易感基因。将小鼠放到室外的围栏中（野化），然后分析其在血液和淋巴结中的免疫反应。免疫细胞群的变异主要受环境影响，而微生物抗原引起的细胞因子产生则受基因突变的影响更大。我们在与T细胞群体差异相关的淋巴结中发现了转录特征。与产气荚膜梭菌，白色念珠菌，寻常型拟杆菌也与野性结合。因此，将具有基因突变的实验室小鼠暴露于自然环境中，发现其对微生物反应和免疫细胞组成变化的不同贡献。

更新日期：2020-03-24

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