CSF-contacting neurons respond to Streptococcus pneumoniae and promote host survival during central nervous system infection

Andrew E. Prendergast, Kin Ki Jim, Hugo Marnas, Laura Desban, Feng B. Quan, Lydia Djenoune, Valerio Laghi, Agnès Hocquemiller, Elias T. Lunsford, Julian Roussel, Ludovic Keiser, Francois-Xavier Lejeune, Mahalakshmi Dhanasekar, Pierre-Luc Bardet, Jean-Pierre Levraud, Diederik van de Beek, Christina M. J. E. Vandenbroucke-Grauls*, Claire Wyart*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


The pathogenic bacterium Streptococcus pneumoniae (S. pneumoniae) can invade the cerebrospinal fluid (CSF) and cause meningitis with devastating consequences. Whether and how sensory cells in the central nervous system (CNS) become activated during bacterial infection, as recently reported for the peripheral nervous system, is not known. We find that CSF infection by S. pneumoniae in larval zebrafish leads to changes in posture and behavior that are reminiscent of pneumococcal meningitis, including dorsal arching and epileptic-like seizures. We show that during infection, invasion of the CSF by S. pneumoniae massively activates in vivo sensory neurons contacting the CSF, referred to as “CSF-cNs” and previously shown to detect spinal curvature and to control posture, locomotion, and spine morphogenesis. We find that CSF-cNs express orphan bitter taste receptors and respond in vitro to bacterial supernatant and metabolites via massive calcium transients, similar to the ones observed in vivo during infection. Upon infection, CSF-cNs also upregulate the expression of numerous cytokines and complement components involved in innate immunity. Accordingly, we demonstrate, using cell-specific ablation and blockade of neurotransmission, that CSF-cN neurosecretion enhances survival of the host during S. pneumoniae infection. Finally, we show that CSF-cNs respond to various pathogenic bacteria causing meningitis in humans, as well as to the supernatant of cells infected by a neurotropic virus. Altogether, our work uncovers that central sensory neurons in the spinal cord, previously involved in postural control and morphogenesis, contribute as well to host survival by responding to the invasion of the CSF by pathogenic bacteria during meningitis.
Original languageEnglish
Pages (from-to)940-956.e10
JournalCurrent Biology
Issue number5
Early online date2023
Publication statusPublished - 13 Mar 2023

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