Regulation of neonatal IgA production by the maternal microbiota.

Regulation of neonatal IgA production by the maternal microbiota.
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DOI:
10.1073/pnas.2015691118
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发表时间:
2021-03-02
影响因子:
11.1
通讯作者:
Luo XM
Luo XM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mu Q;Swartwout BK;Edwards M;Zhu J;Lee G;Eden K;Cabana-Puig X;McDaniel DK;Mao J;Abdelhamid L;Brock RM;Allen IC;Reilly CM;Luo XM

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婴儿出生时没有既定的肠道微生物群,出生后迅速发育,并由母体微生物群塑造。然而,母体微生物群如何通过塑造新生儿微生物群来影响新生儿建立强大的免疫系统仍不清楚。在这里,我们机械地展示了母体微生物群如何调节新生儿伊加的从头产生。由于免疫系统发育不全,婴儿容易患肠道感染。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。我们和其他人已经观察到的现象,增强早期新生儿免疫球蛋白A(伊加)生产断奶前免疫功能正常的小鼠由免疫缺陷的母鼠。在这里,我们表明新生儿中伊加的这种增强是由母体来源的微生物群引起的。此外,我们已经发现,新生儿伊加的生产可以诱导罗伊氏乳杆菌,这是丰富的免疫缺陷母鼠的牛奶。此外,我们表明,虽然新生儿伊加的产生依赖于新生儿T细胞,但免疫缺陷母体微生物群介导的新生儿伊加增强具有不依赖于T细胞的成分。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伊加不与常见的肠道病原体交叉反应。未来的研究将确定具有这种额外伊加的功能后果。
Infants are born without an established gut microbiota, which develops rapidly after birth and is shaped by the maternal microbiota. However, how the maternal microbiota, through shaping the neonatal microbiota, would affect the establishment of a strong immune system in neonates remains unclear. Here, we show mechanistically how the maternal microbiota regulates the de novo production of neonatal IgA. 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 Lactobacillus reuteri, 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.
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