rigeminal TRPV1 regulates pneumococcal nose-to-brain invasion via IL-6/TNF-α signals
Le résumé fourni par la source
The nasal cavity acts as a gateway through which pathogens can invade the human body. Streptococcus pneumoniae can infect the central nervous system directly through the nasal cavity. However, the regulatory mechanisms that govern the direct nose-to-brain invasion of S. pneumoniae remain unclear. The nasal cavity is innervated by both olfactory and trigeminal nerves, which will modulate the defense mechanism of the olfactory epithelium in different ways. Transient receptor potential vanilloid 1 (TRPV1), which is expressed in both nerves, maintains the regeneration ability of the olfactory epithelium. In this study, we investigated the role of TRPV1 against the nose-to-brain invasion of S. pneumoniae. Six-week-old mice were treated with methimazole and/or resiniferatoxin to ablate TRPV1 on the olfactory and trigeminal nerves, respectively. Bacterial density, cytokines/chemokine induction, and histologic changes were investigated after intranasal infection with S. pneumoniae. Olfactory epithelium ablation by methimazole increased intracranial invasion and mortality without bacteremia. Trigeminal TRPV1 ablation suppressed mortality. Intracranial invasion of S. pneumoniae induced IL-6 in the olfactory bulb. Olfactory epithelium ablation was associated with significantly higher TNF-α compared to trigeminal TRPV1 ablation. Intracranial invasion was suppressed by intranasal administration of a TRPV1 stimulant. TRPV1 on the olfactory nerve worked against intracranial invasion, whereas TRPV1 on the trigeminal nerve enhanced lethality via excessive cytokine/chemokine production. The effect of intranasal TRPV1 stimulation was dominant on the olfactory nerve and could suppress central nervous system infection via the nose-to-brain route. The current finding can bring new strategies against infection targeting TRPV1.
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