RRC ID 81483
Author Fioriti F, Rifflet A, Gomperts Boneca I, Zugasti O, Royet J.
Title Bacterial peptidoglycan serves as a critical modulator of the gut-immune-brain axis in Drosophila.
Journal Brain Behav Immun
Abstract Metabolites and compounds derived from gut-associated bacteria can modulate numerous physiological processes in the host, including immunity and behavior. Using a model of oral bacterial infection, we previously demonstrated that gut-derived peptidoglycan (PGN), an essential constituent of the bacterial cell envelope, influences female fruit fly egg-laying behavior by activating the NF-κB cascade in a subset of brain neurons. These findings underscore PGN as a potential mediator of communication between gut bacteria and the brain in Drosophila, prompting further investigation into its impact on all brain cells. Through high-resolution mass spectrometry, we now show that PGN fragments produced by gut bacteria can rapidly reach the central nervous system. In Addition, by employing a combination of whole-genome transcriptome analyses, comprehensive genetic assays, and reporter gene systems, we reveal that gut bacterial infection triggers a PGN dose-dependent NF-κB immune response in perineurial glia, forming the continuous outer cell layer of the blood-brain barrier. Furthermore, we demonstrate that persistent PGN-dependent NF-κB activation in perineurial glial cells correlates with a reduction in lifespan and early neurological decline. Overall, our findings establish gut-derived PGN as a critical mediator of the gut-immune-brain axis in Drosophila.
Volume 119
Pages 878-897
Published 2024-7-1
DOI 10.1016/j.bbi.2024.05.009
PII S0889-1591(24)00398-2
PMID 38710338
MeSH Animals Blood-Brain Barrier / immunology Blood-Brain Barrier / metabolism Brain* / immunology Brain* / metabolism Brain-Gut Axis* / physiology Drosophila Drosophila Proteins / metabolism Drosophila melanogaster / metabolism Female Gastrointestinal Microbiome* / physiology NF-kappa B* / metabolism Neuroglia / immunology Neuroglia / metabolism Neurons / metabolism Peptidoglycan* / metabolism
Resource
Drosophila DGRC#103953 DGRC#105240 DGRC#112830 DGRC#103953