Bitter taste signaling in tracheal epithelial brush cells elicits innate immune responses to bacterial infection

Hollenhorst, Monika I.; Nandigama, Rajender; Evers, Saskia B.; Gamayun, Igor; Wadood, Noran Abdel; Salah, Alaa; Pieper, Mario; Wyatt, Amanda; Stukalov, Alexey; Gebhardt, Anna; Nadolni, Wiebke; Burow, Wera; Herr, Christian; Beißwenger, Christoph; Kusumakshi, Soumya; Ectors, Fabien; Kichko, Tatjana I.; Hübner, L.; Reeh, Peter W.; Munder, Antje; Wienhold, Sandra-Maria; Witzenrath, Martin; Bals, Robert; Flockerzi, Veit; Gudermann, Thomas; Bischoff, Markus; Lipp, Peter; Zierler, Susanna; Chubanov, Vladimir; Pichlmair, Andreas; König, Peter; Boehm, Ulrich; Krasteva‐Christ, Gabriela

doi:10.1172/jci150951

Cited by 24 publications

(41 citation statements)

References 81 publications

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“…It is intriguing to speculate on the activating signals and receptors that direct brush cells to initiate protective responses to expel bacteria or to promote chronic type 2 inflammation. The findings in Hollenhorst, Nandigama, et al add to the growing body of literature indicating that the activation of taste receptors on tracheal brush cells leads to acetylcholine release, which promotes most of the protective brush cellinitiated responses, including increased mucociliary clearance, respiratory reflexes, and vascular permeability with extravasation of neutrophils (4,9,17). neutrophil influx and vascular permeability, in agreement with other studies (12).…”

Section: Paracrine Secretion and The Response To Specific Stimulisupporting

confidence: 81%

“…As bacteria such as P. aeruginosa use QSMs to communicate and increase numbers and virulence, the brush cell recognition system might serve as a sensor of impending bacterial invasion. Consistently, the authors demonstrated decreased lung inflammation and improved survival when bitter-taste signaling was disrupted in mice infected with very low-dose P. aeruginosa (9).…”

Section: Mucosal Immunity and Host Defensementioning

confidence: 59%

“…Interestingly, Hollenhorst, Nandigama, et al also found that bitter-taste receptor ligands trigger the release and accumulation of endopeptidases and complement components in the subepithelial compartments of tracheas (9). Incubation of P. aeruginosa cultures with these tracheal supernatants had a bacteriostatic effect.…”

Section: Paracrine Secretion and The Response To Specific Stimulimentioning

confidence: 97%

“…In this issue of the JCI, Hollenhorst, Nandigama, et al uncovered how brush cells direct the mucosal host defense to impending Pseudomonas aeruginosa infection (9). Brush cells are activated by bitter-tasting substances, including several quorum-sensing molecules (QSMs) from P. aeruginosa.…”

Section: Mucosal Immunity and Host Defensementioning

confidence: 99%

“…Hollenhorst, Nandigama, et al (9) demonstrated that tracheal brush cells detected bacterial metabolites, especially those that…”

Section: Conclusion and Clinical Implicationsmentioning

confidence: 99%

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Brush cells fine-tune neurogenic inflammation in the airways

Ye¹,

Bankova²

2022

Journal of Clinical Investigation

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Section: Paracrine Secretion and The Response To Specific Stimulisupporting

confidence: 81%

Section: Mucosal Immunity and Host Defensementioning

confidence: 59%

Section: Paracrine Secretion and The Response To Specific Stimulimentioning

confidence: 97%

Section: Mucosal Immunity and Host Defensementioning

confidence: 99%

“…Hollenhorst, Nandigama, et al (9) demonstrated that tracheal brush cells detected bacterial metabolites, especially those that…”

Section: Conclusion and Clinical Implicationsmentioning

confidence: 99%

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Brush cells fine-tune neurogenic inflammation in the airways

Ye¹,

Bankova²

2022

Journal of Clinical Investigation

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The pulmonary neuroepithelial body microenvironment represents an underestimated multimodal component in airway sensory pathways

Brouns

Adriaensen

Timmermans

2023

The Anatomical Record

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Exciting new imaging and molecular tools, combined with state‐of‐the‐art genetically modified mouse models, have recently boosted interest in pulmonary (vagal) sensory pathway investigations. In addition to the identification of diverse sensory neuronal subtypes, visualization of intrapulmonary projection patterns attracted renewed attention on morphologically identified sensory receptor end‐organs, such as the pulmonary neuroepithelial bodies (NEBs) that have been our area of expertise for the past four decades. The current review aims at providing an overview of the cellular and neuronal components of the pulmonary NEB microenvironment (NEB ME) in mice, underpinning the role of these complexly organized structures in the mechano‐ and chemosensory potential of airways and lungs. Interestingly, the pulmonary NEB ME additionally harbors different types of stem cells, and emerging evidence suggests that the signal transduction pathways that are active in the NEB ME during lung development and repair also determine the origin of small cell lung carcinoma. Although documented for many years that NEBs appear to be affected in several pulmonary diseases, the current intriguing knowledge on the NEB ME seems to encourage researchers that are new to the field to explore the possibility that these versatile sensor‐effector units may be involved in lung pathogenesis or pathobiology.

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Neuroimmune pathways regulating airway inflammation

Trevizan‐Baú

Mazzone

2023

Annals of Allergy, Asthma & Immunology

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Bitter taste signaling in tracheal epithelial brush cells elicits innate immune responses to bacterial infection

Cited by 24 publications

References 81 publications

Brush cells fine-tune neurogenic inflammation in the airways

Brush cells fine-tune neurogenic inflammation in the airways

The pulmonary neuroepithelial body microenvironment represents an underestimated multimodal component in airway sensory pathways

Neuroimmune pathways regulating airway inflammation

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