An in vivo brain–bacteria interface: the developing brain as a key regulator of innate immunity
| Autor: | Alina Fischer, Sophia K. Jannetty, Celia Herrera-Rincon, Michael Levin, Richard M. Novak, Christina Harrison, Christopher J. Martyniuk, Alexandre L. M. Dinis, Jean-François Paré, Vishal Keshari |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunology Biomedical Engineering Xenopus Regulator Medicine (miscellaneous) lcsh:Medicine Article 03 medical and health sciences 0302 clinical medicine Immune system In vivo Innate immune system biology lcsh:R Cell Biology biology.organism_classification Embryonic stem cell 3. Good health Cell biology Crosstalk (biology) 030104 developmental biology Apoptosis 030217 neurology & neurosurgery Developmental Biology Neuroscience |
| Zdroj: | npj Regenerative Medicine, Vol 5, Iss 1, Pp 1-18 (2020) NPJ Regenerative Medicine |
| ISSN: | 2057-3995 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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