Central Sensory Neurons Detect and Combat Pathogens Invading the Cerebrospinal Fluid

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.