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Central Sensory Neurons Detect and Combat Pathogens Invading the Cerebrospinal Fluid

51 Pages Posted: 17 Jun 2019 Sneak Peek Status: Review Complete

See all articles by Andrew Prendergast

Andrew Prendergast

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

Kin Ki Jim

VU University Amsterdam - Neuroscience Campus Amsterdam

Hugo Marnas

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

Laura Desban

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

Feng Quan

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

Lydia Djenoune

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

Julian Roussel

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

Yasmine Cantaut-Belarif

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

Shubham Sahu

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

Pierre-Luc Bardet

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

Diederik van de Beek

University of Amsterdam - Department of Neurology

Christina Vandenbroucke-Grauls

University of Amsterdam - University Medical Center

Claire Wyart

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

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Abstract

Pathogenic bacteria can infect the central nervous system via the cerebrospinal fluid (CSF), leading to devastating consequences. How pathogens are detected and eliminated from the CSF is incompletely understood, though resident and circulating immune cells certainly contribute. To address this question, we infected zebrafish larvae with different bacteria that cause meningitis in humans. Unexpectedly, we observed a striking activation of sensory neurons contacting the CSF (“CSF-cNs”) after infection in vivo. In vitro, CSF-cNs were activated by factors secreted by bacteria, such as cytolysins and bitter compounds. Accordingly, we show that CSF-cNs selectively express orphan taste receptors along with antimicrobial peptides and chemoattractant factors that act on peripheral blood monocytes. Selective ablation of CSF-cNs or inhibition of their neurosecretion reduced host survival upon infection. The discovery that central sensory neurons detect bacteria, enhance host defense, and actively combat pathogens implies new targets for the treatment of bacterial meningitis.

Keywords: Central nervous system, Sensory neurons, Interoception, Pathogen detection, Cerebrospinal fluid, Innate immunity, Host defense, Neurosecretion, Peptides, Cytolysins, Taste receptors, Bacterial meningitis.

Suggested Citation

Prendergast, Andrew and Jim, Kin Ki and Marnas, Hugo and Desban, Laura and Quan, Feng and Djenoune, Lydia and Roussel, Julian and Cantaut-Belarif, Yasmine and Sahu, Shubham and Bardet, Pierre-Luc and van de Beek, Diederik and Vandenbroucke-Grauls, Christina and Wyart, Claire, Central Sensory Neurons Detect and Combat Pathogens Invading the Cerebrospinal Fluid (June 14, 2019). Available at SSRN: https://ssrn.com/abstract=3404255 or http://dx.doi.org/10.2139/ssrn.3404255
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Andrew Prendergast

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

175 Rue du Chevaleret
Paris, 75013
France

Kin Ki Jim

VU University Amsterdam - Neuroscience Campus Amsterdam ( email )

Amsterdam
Netherlands

Hugo Marnas

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

175 Rue du Chevaleret
Paris, 75013
France

Laura Desban

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

175 Rue du Chevaleret
Paris, 75013
France

Feng Quan

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

175 Rue du Chevaleret
Paris, 75013
France

Lydia Djenoune

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

175 Rue du Chevaleret
Paris, 75013
France

Julian Roussel

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

175 Rue du Chevaleret
Paris, 75013
France

Yasmine Cantaut-Belarif

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

175 Rue du Chevaleret
Paris, 75013
France

Shubham Sahu

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

175 Rue du Chevaleret
Paris, 75013
France

Pierre-Luc Bardet

Sorbonne Universités - Institut du cerveau et la moelle (ICM)

175 Rue du Chevaleret
Paris, 75013
France

Diederik Van de Beek

University of Amsterdam - Department of Neurology ( email )

Spui 21
Amsterdam, 1018 WB
Netherlands

Christina Vandenbroucke-Grauls

University of Amsterdam - University Medical Center

Meibergdreef 9
Amsterdam, 1105
Netherlands

Claire Wyart (Contact Author)

Sorbonne Universités - Institut du cerveau et la moelle (ICM) ( email )

175 Rue du Chevaleret
Paris, 75013
France

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