| First Author | Bin NR | Year | 2023 |
| Journal | Nature | Volume | 615 |
| Issue | 7953 | Pages | 660-667 |
| PubMed ID | 36890237 | Mgi Jnum | J:340489 |
| Mgi Id | MGI:7525525 | Doi | 10.1038/s41586-023-05796-0 |
| Citation | Bin NR, et al. (2023) An airway-to-brain sensory pathway mediates influenza-induced sickness. Nature 615(7953):660-667 |
| abstractText | Pathogen infection causes a stereotyped state of sickness that involves neuronally orchestrated behavioural and physiological changes(1,2). On infection, immune cells release a 'storm' of cytokines and other mediators, many of which are detected by neurons(3,4); yet, the responding neural circuits and neuro-immune interaction mechanisms that evoke sickness behaviour during naturalistic infections remain unclear. Over-the-counter medications such as aspirin and ibuprofen are widely used to alleviate sickness and act by blocking prostaglandin E2 (PGE2) synthesis(5). A leading model is that PGE2 crosses the blood-brain barrier and directly engages hypothalamic neurons(2). Here, using genetic tools that broadly cover a peripheral sensory neuron atlas, we instead identified a small population of PGE2-detecting glossopharyngeal sensory neurons (petrosal GABRA1 neurons) that are essential for influenza-induced sickness behaviour in mice. Ablating petrosal GABRA1 neurons or targeted knockout of PGE2 receptor 3 (EP3) in these neurons eliminates influenza-induced decreases in food intake, water intake and mobility during early-stage infection and improves survival. Genetically guided anatomical mapping revealed that petrosal GABRA1 neurons project to mucosal regions of the nasopharynx with increased expression of cyclooxygenase-2 after infection, and also display a specific axonal targeting pattern in the brainstem. Together, these findings reveal a primary airway-to-brain sensory pathway that detects locally produced prostaglandins and mediates systemic sickness responses to respiratory virus infection. |
