How the brain senses a flu infection — and orders the body to rest - Nature

[Mary Wilson]

Scientists trace the neurons in the throat that detect signs of infection and relay this information to the brain.

08 March 2023
Liam Drew

... scientists have identified neurons in mice that notify the brain of a flu infection, triggering decreases in movement, hunger and thirst[SUP]1[/SUP].
Similar neurons connecting to other parts of the body might notify the brain of other infections, too, the authors say. The work was published on 8 March in Nature.

... Before this research, “it was not clear how the brain becomes aware that there’s an infection in the body”, says study co-author Stephen Liberles, a neuroscientist at Harvard Medical School in Boston, Massachusetts. Scientists generally thought that messenger molecules from the site of infection move through the bloodstream to the brain, diffusing into it to directly activate the regions that kickstart the sickness-behaviour program.

... the authors found that the key agents are a specific EP3-containing population of neurons located in the mouse’s neck. These neurons have branches that stretch from the mouse equivalent of the tonsils to the brainstem. This geography makes sense: the tonsil area “serves as the interface between the outside air and what goes in the airway”, says study co-author Na-Ryum Bin, a neurobiologist also at Harvard. The area is rich in immune cells that churn out prostaglandins when they encounter pathogens.

https://www.nature.com/articles/d41586-023-00675-0

 

[Mary Wilson]

An airway-to-brain sensory pathway mediates influenza-induced sickness

Published: 08 March 2023

DOI https://doi.org/10.1038/s41586-023-05796-0

Na-Ryum Bin, Sara L. Prescott, Nao Horio, Yandan Wang, Isaac M. Chiu & Stephen D. Liberles

Abstract

Pathogen infection causes a stereotyped state of sickness that involves neuronally orchestrated behavioural and physiological changes[SUP]1,2[/SUP]. On infection, immune cells release a ‘storm’ of cytokines and other mediators, many of which are detected by neurons[SUP]3,4[/SUP]; 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[SUP]5[/SUP]. A leading model is that PGE2 crosses the blood–brain barrier and directly engages hypothalamic neurons[SUP]2[/SUP]. 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.

https://www.nature.com/articles/s41586-023-05796-0#citeas