Spleen development is modulated by neonatal gut microbiota
Spleen development is modulated by neonatal gut microbiota
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DOI：
10.1016/j.imlet.2018.04.010
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发表时间：
2018-07-01
影响因子：
4.4
通讯作者：
Carsetti, Rita
中科院分区：
文献类型：
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作者：
Rosado, M. Manuela;Aranburu, Alaitz;Carsetti, Rita
哺乳动物免疫系统的全面发育是在出生后接触非自身抗原时发生的。肠道是细菌定植的第一个场所，创造适当的微环境至关重要，能够平衡对外部刺激的效应或耐受性反应。众所周知的事实是，在粘膜部位，细菌在免疫系统的发育中发挥着关键作用，但我们忽略了定植细菌如何影响脾脏的成熟。在这里我们解决了这个问题。利用牛奶 SIgA 调节新生肠道细菌定植的事实，我们培育了具有 IgA 高效或 IgA 缺陷的雌性小鼠，产生了具有免疫功能的小鼠。在证明母乳中的 SIgA 通过促进定植物种多样性的增加来调节新生儿肠道微生物群后，我们还发现，免疫功能健全的幼崽，如果没有接触乳汁 SIgA，则无法正确发育脾脏中的 FDC 网络和初级滤泡，从而损害对 T 依赖性抗原的反应。微生物群多样性较低且致病物种代表性较高，导致脾脏边缘区和 IgM 浆细胞区室以及肠道中 IgA 浆细胞的快速补充。
The full development of the mammalian immune system occurs after birth upon exposure to non self-antigens. The gut is the first site of bacterial colonization where it is crucial to create the appropriate microenvironment able to balance effector or tolerogenic responses to external stimuli. It is a well-established fact that at mucosal sites bacteria play a key role in developing the immune system but we ignore how colonising bacteria impact the maturation of the spleen. Here we addressed this issue. Taking advantage of the fact that milk SIgA regulates bacterial colonization of the newborn intestine, we generated immunocompetent mice born either from IgA pro-efficient or IgA deficient females. Having demonstrated that SIgA in maternal milk modulates neonatal gut microbiota by promoting an increased diversity of the colonizing species we also found that immunocompetent pups, not exposed to milk SIgA, fail to properly develop the FDC network and primary follicles in the spleen compromising the response to T-dependent antigens. The presence of a less diverse microbiota with a higher representation of pathogenic species leads to a fast replenishment of the marginal zone and the IgM plasma cell compartment of the spleen as well as IgA plasma cells in the gut.