Department of Inflammation and Immunity, Learner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250000, P.R. China; College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, P.R. China.
Department of Inflammation and Immunity, Learner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Cell Host Microbe. 2023 Oct 11;31(10):1620-1638.e7. doi: 10.1016/j.chom.2023.09.001. Epub 2023 Sep 29.
Immunoglobulin A (IgA) is an important factor in maintaining homeostasis at mucosal surfaces, yet luminal IgA levels vary widely. Total IgA levels are thought to be driven by individual immune responses to specific microbes. Here, we found that the prebiotic, pectin oligosaccharide (pec-oligo), induced high IgA levels in the small intestine in a T cell-dependent manner. Surprisingly, this IgA-high phenotype was retained after cessation of pec-oligo treatment, and microbiome transmission either horizontally or vertically was sufficient to retain high IgA levels in the absence of pec-oligo. Interestingly, the bacterial taxa enriched in the overall pec-oligo bacterial community differed from IgA-coated microbes in this same community. Rather, a group of ethanol-resistant microbes, highly enriched for Lachnospiraceae bacterium A2, drove the IgA-high phenotype. These findings support a model of intestinal adaptive immunity in which a limited number of microbes can promote durable changes in IgA directed to many symbionts.
免疫球蛋白 A(IgA)是维持黏膜表面内环境稳定的重要因素,但腔道内 IgA 水平差异很大。总 IgA 水平被认为是个体对特定微生物的免疫反应所驱动。在这里,我们发现,益生元果胶寡糖(pec-oligo)以 T 细胞依赖的方式诱导小肠中产生高 IgA 水平。令人惊讶的是,这种 IgA 高表型在停止 pec-oligo 治疗后仍然存在,并且微生物组的水平或垂直传播足以在没有 pec-oligo 的情况下保留高 IgA 水平。有趣的是,在整个 pec-oligo 细菌群落中富集的细菌分类群与同一群落中 IgA 包被的微生物不同。相反,一群耐乙醇的微生物,富含lachnospiraceae 细菌 A2,驱动了 IgA 高表型。这些发现支持了肠道适应性免疫的模型,即少数微生物可以促进针对许多共生体的 IgA 的持久变化。