Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Cell Host Microbe. 2020 Mar 11;27(3):467-475.e6. doi: 10.1016/j.chom.2020.01.016. Epub 2020 Feb 18.
Fecal IgA production depends on colonization by a gut microbiota. However, the bacterial strains that drive gut IgA production remain largely unknown. Here, we assessed the IgA-inducing capacity of a diverse set of human gut microbial strains by monocolonizing mice with each strain. We identified Bacteroides ovatus as the species that best induced gut IgA production. However, this induction varied bimodally across different B. ovatus strains. The high IgA-inducing B. ovatus strains preferentially elicited more IgA production in the large intestine through the T cell-dependent B cell-activation pathway. Remarkably, a low-IgA phenotype in mice could be robustly and consistently converted into a high-IgA phenotype by transplanting a multiplex cocktail of high IgA-inducing B. ovatus strains but not individual ones. Our results highlight the critical importance of microbial strains in driving phenotype variation in the mucosal immune system and provide a strategy to robustly modify a gut immune phenotype, including IgA production.
粪便 IgA 的产生依赖于肠道微生物群的定植。然而，驱动肠道 IgA 产生的细菌菌株在很大程度上仍是未知的。在这里，我们通过用每种菌株单定植小鼠来评估一组多样化的人类肠道微生物菌株的 IgA 诱导能力。我们发现卵形拟杆菌是诱导肠道 IgA 产生的最佳物种。然而，这种诱导在不同的卵形拟杆菌菌株之间呈双峰分布。高 IgA 诱导的卵形拟杆菌菌株通过依赖于 T 细胞的 B 细胞激活途径优先在大肠中引起更多的 IgA 产生。值得注意的是，通过移植高 IgA 诱导的卵形拟杆菌菌株的多重混合物而不是单个菌株，可以将小鼠中的低 IgA 表型稳健且一致地转化为高 IgA 表型。我们的结果强调了微生物菌株在驱动黏膜免疫系统表型变异方面的重要性，并提供了一种稳健地修饰肠道免疫表型（包括 IgA 产生）的策略。
