Combined effect of BCG vaccination and enriched environment promote neurogenesis and spatial cognition via a shift in meningeal macrophage M2 polarization.
Combined effect of BCG vaccination and enriched environment promote neurogenesis and spatial cognition via a shift in meningeal macrophage M2 polarization.
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BCG 疫苗接种和丰富环境的联合作用通过脑膜巨噬细胞 M2 极化的转变促进神经发生和空间认知
DOI：
10.1186/s12974-017-0808-7
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发表时间：
2017-02-10
影响因子：
9.3
通讯作者：
Yao Z
中科院分区：
文献类型：
--
作者：
Qi F;Zuo Z;Yang J;Hu S;Yang Y;Yuan Q;Zou J;Guo K;Yao Z
发育中的小鼠的空间学习能力受益于外部线索，例如丰富的环境，同时认知功能也得到增强。有趣的是，通过内在的卡介苗（BCG）接种，这种增强作用可以进一步提高。
在此，我们首次报道，在暴露于丰富环境（Enr）的小鼠中，新生期卡介苗接种与丰富环境暴露相结合诱导了综合的神经有益效应，包括海马长时程增强，以及神经发生和空间学习记忆能力的提高，相对于未接种卡介苗的处于丰富环境中的小鼠而言。新生期卡介苗接种在常规饲养和丰富环境饲养的小鼠中均显著诱导抗炎性脑膜巨噬细胞极化。脑膜由软脑膜、硬脑膜和脉络丛组成。或者说，脑膜的这种抗炎活性与海马中神经营养因子脑源性神经营养因子（BDNF）/胰岛素样生长因子 - 1（IGF - 1）的表达增加以及小胶质细胞M2表型同时发生。我们的研究结果揭示了卡介苗接种通过脑膜巨噬细胞M2极化和神经营养因子表达在神经发生和空间认知调节中的关键作用；这些效应分别被米诺环素或抗白细胞介素 - 10抗体处理完全或部分阻断。
总之，我们首次提出免疫因素和环境因素通过一个共同途径——脑膜巨噬细胞M2极化对神经发生和认知产生联合作用。我们还提出了在外周引发适应性免疫反应后外周T淋巴细胞和脑膜巨噬细胞之间一种新的功能关联，即T淋巴细胞响应全身性干扰素 - γ信号被募集到脑膜。这导致脑膜巨噬细胞M2极化，继而是小胶质细胞M2活化和神经营养因子表达，最终促进积极的行为。
本文的在线版本（doi:10.1186/s12974 - 2017 - 0808 - 7）包含补充材料，可供授权用户使用。
BackgroundThe spatial learning abilities of developing mice benefit from extrinsic cues, such as an enriched environment, with concomitant enhancement in cognitive functions. Interestingly, such enhancements can be further increased through intrinsic Bacillus Calmette-Guérin (BCG) vaccination.ResultsHere, we first report that combined neonatal BCG vaccination and exposure to an enriched environment (Enr) induced combined neurobeneficial effects, including hippocampal long-term potentiation, and increased neurogenesis and spatial learning and memory, in mice exposed to the Enr and vaccinated with BCG relative to those in the Enr that did not receive BCG vaccination. Neonatal BCG vaccination markedly induced anti-inflammatory meningeal macrophage polarization both in regular and Enr breeding mice. The meninges are composed of the pia mater, dura mater, and choroid plexus. Alternatively, this anti-inflammatory activity of the meninges occurred simultaneously with increased expression of the neurotrophic factors BDNF/IGF-1 and the M2 microglial phenotype in the hippocampus. Our results reveal a critical role for BCG vaccination in the regulation of neurogenesis and spatial cognition through meningeal macrophage M2 polarization and neurotrophic factor expression; these effects were completely or partially prevented by minocycline or anti-IL-10 antibody treatment, respectively.ConclusionsTogether, we first claim that immunological factor and environmental factor induce a combined effect on neurogenesis and cognition via a common pathway-meningeal macrophage M2 polarization. We also present a novel functional association between peripheral T lymphocytes and meningeal macrophages after evoking adaptive immune responses in the periphery whereby T lymphocytes are recruited to the meninges in response to systemic IFN-γ signaling. This leads to meningeal macrophage M2 polarization, subsequent to microglial M2 activation and neurotrophic factor expression, and eventually promotes a positive behavior.