Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals

Abstract

The upper respiratory tract is continually assaulted with harmful dusts and xenobiotics carried on the incoming airstream. Detection of such irritants by the trigeminal nerve evokes protective reflexes, including sneezing, apnea, and local neurogenic inflammation of the mucosa. Although free intra-epithelial nerve endings can detect certain lipophilic irritants (e.g., mints, ammonia), the epithelium also houses a population of trigeminally innervated solitary chemosensory cells (SCCs) that express T2R bitter taste receptors along with their downstream signaling components. These SCCs have been postulated to enhance the chemoresponsive capabilities of the trigeminal irritant-detection system. Here we show that transduction by the intranasal solitary chemosensory cells is necessary to evoke trigeminally mediated reflex reactions to some irritants including acyl–homoserine lactone bacterial quorum-sensing molecules, which activate the downstream signaling effectors associated with bitter taste transduction. Isolated nasal chemosensory cells respond to the classic bitter ligand denatonium as well as to the bacterial signals by increasing intracellular Ca 2 + . Furthermore, these same substances evoke changes in respiration indicative of trigeminal activation. Genetic ablation of either Gα-gustducin or TrpM5, essential elements of the T2R transduction cascade, eliminates the trigeminal response. Because acyl–homoserine lactones serve as quorum-sensing molecules for Gram-negative pathogenic bacteria, detection of these substances by airway chemoreceptors offers a means by which the airway epithelium may trigger an epithelial inflammatory response before the bacteria reach population densities capable of forming destructive biofilms.

Bitter triggers acetylcholine release from polymodal urethral chemosensory cells and bladder reflexes

“…In contrast, on other mucosal surfaces, such as the urethral lining, these qualities represent potentially harmful (aversive) content. Bacteria produce and secrete bitter receptor-activating substances (5,37,38). In biofilms, such substances from the Gram-negative bacterium Pseudomonas aeruginosa, one of the predominant causative microorganisms in catheter-associated urinary tract infection (39), can reach concentrations as high as 600 μM (40).…”

“…Respiratory chemosensory brush cells express elements of the canonical taste transduction cascade, including the taste-specific G protein α-gustducin, phospholipase C β2 (PLCβ2), and the transient potential receptor cation channel melanostatin 5 (TRPM5) (5,6,(15)(16)(17). These proteins are also expressed in urethras from ChAT-eGFP and WT mice (Fig.…”

“…In the respiratory tract, these brush cells serve as sentinels, using the canonical taste transduction cascade to monitor the mucosal lining fluid for potential harmful substances, such as "bitter" bacterial products, and evoking reflexes aimed at combating further ingression of such compounds, such as closure of ducts leading into adjacent compartments (vomeronasal organ) or respiratory reflexes (4)(5)(6)(7).…”

Trigeminal Chemesthesis

“…The glossopharyngeal (CN IX) and vagus (CN X) nerves also contribute to chemesthesis in the mouth (posterior tongue) and the nasopharyngeal and pharyngeal (throat) areas. Studies in mice and rats have shown that nasal solitary chemoreceptor cells (SCCs) can contribute to nasal chemesthesis (Finger et al, 2003;Silver and Finger, 2009;Tizzano et al, 2010), although their development and survival does not seem to be dependent on intact trigeminal innervation (Gulbransen et al, 2008a). SCCs express receptor proteins involved in gustatory chemoreception (T1Rs, T2Rs) and, thus, are also related to the sense of taste (Gulbransen et al, 2008b;Ohmoto et al, 2008;Sbarbati et al, 2004;Tizzano et al, 2011).…”

“…SCCs express receptor proteins involved in gustatory chemoreception (T1Rs, T2Rs) and, thus, are also related to the sense of taste (Gulbransen et al, 2008b;Ohmoto et al, 2008;Sbarbati et al, 2004;Tizzano et al, 2011). However, expression of these receptors is thought to enable identification of potentially noxious irritants or pathogenic secretions (Tizzano et al, 2010). SCCs, which have also been described in several organs from the digestive and respiratory systems, have been proposed to be part of a diffuse chemosensory system (Osculati et al, 2007;Sbarbati et al, 2010).…”