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XB-ART-56679
NPJ Regen Med January 1, 2020; 5 2.

An in vivo brain-bacteria interface: the developing brain as a key regulator of innate immunity.

Herrera-Rincon C , Paré JF , Martyniuk CJ , Jannetty SK , Harrison C , Fischer A , Dinis A , Keshari V , Novak R , Levin M .


Abstract
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.

PubMed ID: 32047653
PMC ID: PMC7000827
Article link: NPJ Regen Med
Grant support: [+]
Genes referenced: ctrl itih3 mmp7 nr2e1 slurp1l tub
GO keywords: immune response


Article Images: [+] show captions
References [+] :
Agricola, Identification of genes expressed in the migrating primitive myeloid lineage of Xenopus laevis. 2016, Pubmed, Xenbase


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