Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Cell Host Microbe. 2020 Jun 10;27(6):909-921.e5. doi: 10.1016/j.chom.2020.03.012. Epub 2020 Apr 13.
Immunoglobulin (Ig) A controls host-microbial homeostasis in the gut. IgA recognition of beneficial bacteria is decreased in acutely undernourished children, but the factors driving these changes in IgA targeting are unknown. Child undernutrition is a global health challenge that is exacerbated by poor sanitation and intestinal inflammation. To understand how nutrition impacts immune-microbe interactions, we used a mouse model of undernutrition with or without fecal-oral exposure and assessed IgA-bacterial targeting from weaning to adulthood. In contrast to healthy control mice, undernourished mice fail to develop IgA recognition of intestinal Lactobacillus. Glycan-mediated interactions between Lactobacillus and host antibodies are lost in undernourished mice due to rapid bacterial adaptation. Lactobacillus adaptations occur in direct response to nutritional pressure, independently of host IgA, and are associated with reduced mucosal colonization and with bacterial mutations in carbohydrate processing genes. Together these data indicate that diet-driven bacterial adaptations shape IgA recognition in the gut.
免疫球蛋白（Ig）A 控制着肠道中宿主与微生物的平衡。急性营养不良儿童对有益细菌的 IgA 识别能力下降，但导致 IgA 靶向这些变化的因素尚不清楚。儿童营养不良是一个全球性的健康挑战，卫生条件差和肠道炎症会使其恶化。为了了解营养如何影响免疫-微生物相互作用，我们使用了一种具有或不具有粪-口暴露的营养不良小鼠模型，并从断奶到成年评估了 IgA-细菌靶向。与健康对照小鼠相比，营养不良的小鼠无法发展出对肠道乳杆菌的 IgA 识别。由于细菌的快速适应，营养不良的小鼠中，聚糖介导的乳杆菌与宿主抗体之间的相互作用丧失了。乳杆菌的适应性是对营养压力的直接反应，与宿主 IgA 无关，与粘膜定植减少以及碳水化合物加工基因的细菌突变有关。这些数据表明，饮食驱动的细菌适应性塑造了肠道中的 IgA 识别。
