Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.
Translational Biology, Medicine and Health Graduate Program, Virginia Polytechnic Institute and State University, Roanoke, VA 24016.
Proc Natl Acad Sci U S A. 2021 Mar 2;118(9). doi: 10.1073/pnas.2015691118.
Infants are prone to enteric infections due to an underdeveloped immune system. The maternal microbiota, through shaping the neonatal microbiota, helps establish a strong immune system in infants. We and others have observed the phenomenon of enhanced early neonatal immunoglobulin A (IgA) production in preweaning immunocompetent mice nursed by immunodeficient dams. Here, we show that this enhancement of IgA in neonates results from maternally derived microbiota. In addition, we have found that the neonatal IgA production can be induced by , which is enriched in the milk of immunodeficient dams. Moreover, we show that while the production of neonatal IgA is dependent on neonatal T cells, the immunodeficient maternal microbiota-mediated enhancement of neonatal IgA has a T cell-independent component. Indeed, this enhancement may be dependent on type 3 innate lymphoid cells in the neonatal small intestinal lamina propria. Interestingly, maternal microbiota-induced neonatal IgA does not cross-react with common enteric pathogens. Future investigations will determine the functional consequences of having this extra IgA.
婴儿由于免疫系统尚未发育成熟，容易发生肠道感染。母体微生物群通过塑造新生儿微生物群，帮助婴儿建立强大的免疫系统。我们和其他人观察到，在由免疫缺陷的母鼠喂养的未成熟免疫功能健全的小鼠中，早期新生儿免疫球蛋白 A（IgA）的产生增强。在这里，我们表明，这种新生儿 IgA 的增强是由母体来源的微生物群引起的。此外，我们发现，在免疫缺陷的母鼠的乳汁中富含的，可诱导新生儿 IgA 的产生。此外，我们表明，虽然新生儿 IgA 的产生依赖于新生儿 T 细胞，但免疫缺陷的母体微生物群介导的新生儿 IgA 的增强具有 T 细胞非依赖性成分。事实上，这种增强可能依赖于新生儿小肠固有层中的 3 型先天淋巴细胞。有趣的是，母体微生物群诱导的新生儿 IgA 与常见的肠道病原体没有交叉反应。未来的研究将确定拥有这种额外 IgA 的功能后果。
