Bin NR, Prescott SL, Horio N, Wang Y, Chiu IM, Lib. An airway-to-brain sensory pathway mediates influenza-induced sickness. Nature. 2023 Mar 8
Pathogen infection causes a stereotyped state of sickness that involves neuronally orchestrated behavioural and physiological changes1,2. On infection, immune cells release a ´storm´ of cytokines and other mediators, many of which are detected by neurons3,4; 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) synthesis5. A leading model is that PGE2 crosses the blood-brain barrier and directly engages hypothalamic neurons2. 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.
See Also:
Latest articles in those days:
- Nucleic acid detection and genomic sequence analysis of one H5N1 avian influenza virus from wide birds around Qinghai Lake 1 days ago
- An aggregated dataset of serial morbidity and titer measurements from influenza A virus-infected ferrets 2 days ago
- Structures of H5N1 influenza polymerase with ANP32B reveal mechanisms of genome replication and host adaptation 4 days ago
- Risk assessment of a highly pathogenic H5N1 influenza virus from mink 4 days ago
- Detection of clade 2.3.4.4b highly pathogenic H5N1 influenza virus in New York City 4 days ago
[Go Top] [Close Window]