Intestinal commensal bacteria mediate lung mucosal immunity and promote resistance of newborn mice to infection.
Intestinal commensal bacteria mediate lung mucosal immunity and promote resistance of newborn mice to infection.
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DOI：
10.1126/scitranslmed.aaf9412
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发表时间：
2017-02-08
影响因子：
17.1
通讯作者：
Deshmukh H
中科院分区：
文献类型：
--
作者：
Gray J;Oehrle K;Worthen G;Alenghat T;Whitsett J;Deshmukh H
不成熟的粘膜防御有助于增加新生儿对病原体的易感性。对粘膜免疫的年龄依赖性变化知之甚少，阻碍了感染所致新生儿发病率的改善。在这里，我们报告说，新生小鼠出生后立即暴露于肠道细菌是对细菌性肺炎（新生儿死亡的主要原因）的强大宿主防御所必需的。这一关键窗口的特征在于产生白细胞介素（IL）-22的3组先天淋巴细胞（IL 22 + ILC 3）突然流入新生小鼠的肺中。这种流入依赖于肠粘膜树突状细胞对肠道细菌的感知。破坏出生后的肠道定植或选择性耗尽树突状细胞中断了肺IL-22+ ILC 3的迁移程序，使新生小鼠更容易患肺炎，出生后肠道细菌的转移可以逆转肺炎。因此，新生小鼠对肺炎的抵抗力依赖于细菌介导的ILC 3流入肺部，其在该发育窗口期间介导IL-22依赖性宿主对肺炎的抵抗力。这些数据表明，出生后肠道细菌的定植在小鼠肺防御的发展中是关键的。
Immature mucosal defenses contribute to increased susceptibility of newborn infants to pathogens. Sparse knowledge of age-dependent changes in mucosal immunity has hampered improvements in neonatal morbidity due to infections. Here, we report that exposure of neonatal mice to commensal bacteria immediately after birth is required for a robust host defense against bacterial pneumonia, the leading cause of death in newborn infants. This crucial window was characterized by an abrupt influx of interleukin (IL)-22 producing group 3 innate lymphoid cells (IL22+ILC3) into the lungs of newborn mice. This influx was dependent on sensing of commensal bacteria by intestinal mucosal dendritic cells. Disruption of postnatal commensal colonization or selective depletion of dendritic cells interrupted the migratory program of lung IL-22+ILC3 and made the newborn mice more susceptible to pneumonia, which was reversed by transfer of commensal bacteria after birth. Thus, the resistance of newborn mice to pneumonia relied on commensal bacteria-directed ILC3-influx into the lungs, which mediated IL-22-dependent host resistance to pneumonia during this developmental window. These data establish that postnatal colonization by intestinal commensal bacteria is pivotal in the development of lung defenses in mice.
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