PUBLICATION
CSF-contacting neurons respond to Streptococcus pneumoniae and promote host survival during central nervous system infection
- Authors
- Prendergast, A.E., Jim, K.K., Marnas, H., Desban, L., Quan, F.B., Djenoune, L., Laghi, V., Hocquemiller, A., Lunsford, E.T., Roussel, J., Keiser, L., Lejeune, F.X., Dhanasekar, M., Bardet, P.L., Levraud, J.P., van de Beek, D., Vandenbroucke-Grauls, C.M.J.E., Wyart, C.
- ID
- ZDB-PUB-230216-33
- Date
- 2023
- Source
- Current biology : CB 33(5): 940-956.e10 (Journal)
- Registered Authors
- Djenoune, Lydia, Laghi, Valerio, Prendergast, Andrew, Wyart, Claire
- Keywords
- bacterial meningitis, bitter compounds, central nervous system infection, cerebrospinal fluid, cytokines, cytolysins, host defense, innate immunity, interoception, neurosecretion, pathogen detection, peptides, sensory neurons, taste receptors
- MeSH Terms
-
- Animals
- Central Nervous System
- Central Nervous System Infections*
- Humans
- Sensory Receptor Cells/physiology
- Streptococcus pneumoniae*/physiology
- Zebrafish/physiology
- PubMed
- 36791723 Full text @ Curr. Biol.
Citation
Prendergast, A.E., Jim, K.K., Marnas, H., Desban, L., Quan, F.B., Djenoune, L., Laghi, V., Hocquemiller, A., Lunsford, E.T., Roussel, J., Keiser, L., Lejeune, F.X., Dhanasekar, M., Bardet, P.L., Levraud, J.P., van de Beek, D., Vandenbroucke-Grauls, C.M.J.E., Wyart, C. (2023) CSF-contacting neurons respond to Streptococcus pneumoniae and promote host survival during central nervous system infection. Current biology : CB. 33(5):940-956.e10.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping