Infections have numerous effects on the brain. However, possible roles of the brain in protecting against infection, and the developmental origin and role of brain signaling in immune response, are largely unknown. We exploited a unique Xenopus embryonic model to reveal control of innate immune response to pathogenic E. coli by the developing brain. Using survival assays, morphological analysis of innate immune cells and apoptosis, and RNA-seq, we analyzed combinations of infection, brain removal, and tail-regenerative response. Without a brain, survival of embryos injected with bacteria decreased significantly. The protective effect of the developing brain was mediated by decrease of the infection-induced damage and of apoptosis, and increase of macrophage migration, as well as suppression of the transcriptional consequences of the infection, all of which decrease susceptibility to pathogen. Functional and pharmacological assays implicated dopamine signaling in the bacteria-brain-immune crosstalk. Our data establish a model that reveals the very early brain to be a central player in innate immunity, identify the developmental origins of brain-immune interactions, and suggest several targets for immune therapies.

中文翻译：

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体内脑细菌界面：发育中的大脑是先天免疫的关键调节因子。

感染对大脑有多种作用。然而，大脑在预防感染中可能发挥的作用，以及大脑信号在免疫应答中的发展起源和作用，目前尚不清楚。我们利用独特的非洲爪蟾胚胎模型来揭示发育中的大脑对病原性大肠杆菌的固有免疫反应的控制。使用存活测定，先天免疫细胞的形态学分析和凋亡以及RNA-seq，我们分析了感染，脑切除和尾部再生反应的组合。没有大脑，注射细菌的胚胎的存活率显着下降。发育中的大脑的保护作用是通过减少感染引起的损伤和凋亡，增加巨噬细胞迁移以及抑制感染的转录结果来介导的，所有这些都降低了对病原体的敏感性。功能和药理分析牵涉到细菌脑免疫串扰中的多巴胺信号传导。我们的数据建立了一个模型，该模型揭示了早期的大脑在先天免疫中起着重要作用，确定了大脑与免疫相互作用的发展起源，并提出了免疫疗法的几个目标。