A century ago, Kolmer and Agduhr identified ciliated neurons in the spinal cord that contact cerebrospinal fluid (CSF) across vertebrate species. These neurons, called spinal CSF-contacting neurons (CSF-cNs), modulate locomotion and posture by detecting mechanical and chemical cues from the CSF. However, the mechanisms by which CSF-cNs detect and respond to CSF changes are unknown. In this study, we investigate whether CSF-cNs in larval zebrafish can detect and respond to pathological CSF changes induced by a ventricular injection of Streptococcus pneumoniae (S. pneumoniae), the major pathogen causing bacterial meningitis in humans. Using calcium imaging, we find that CSF-cNs in vivo detect and respond to bacterial invasion of the CSF. Cell-specific ablation demonstrates that CSF-cNs contribute to the host's survival. In vitro experiments reveal that CSF-cNs robustly respond to metabolites released by S. pneumoniae. Transcriptome analysis of spinal CSF-cNs shows expression of chemoreceptor genes, suggesting a chemosensory role in CSF physiology. We currently characterize receptor expression in CSF-cNs using Hybridization Chain Reaction (HCR) and test in vitro whether specific receptors can elicit calcium signaling. Our work uncovers the ability of CSF-cNs to respond to pathogens by detecting chemical compounds in the CSF, reinforcing host defense. Identifying the receptors and their agonists will enhance understanding of CSF-cN activation mechanisms. Future studies will focus on unraveling downstream signaling pathways involved in innate immunity to promote host defense.