Role of Taste Receptors as Sentinels of Innate Immunity in the Upper Airway

Patel, Neil N.; Workman, Alan D.; Cohen, Noam A.

doi:10.1155/2018/9541987

Cited by 27 publications

(40 citation statements)

References 78 publications

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“…Surprisingly, among the four most ubiquitous enriched pathways for ACE2 and/or TMPRSS2-correlated genes, we found olfactory and taste transduction. Both OR and TAS genes occur in "ectopic" locations within and outside the brain, and could play roles other than odor or taste perception, such as the sensing of peripheral metabolites by hypothalamic tanycytes (53)(54)(55) or the mediation of viral infection or the host response (56,57), and could be over-or under-expressed in disorders like obesity or diabetes (58).…”

Section: Discussionmentioning

confidence: 99%

The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis

Nampoothiri

Sauvé

Ternier

et al. 2020

Preprint

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Most patients with COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), display neurological symptoms, and respiratory failure in certain cases could be of extrapulmonary origin. Hypothalamic neural circuits play key roles in sex differences, diabetes, hypertension, obesity and aging, all risk factors for severe COVID-19, besides being connected to olfactory/gustative and brainstem cardiorespiratory centers. Here, human brain gene-expression analyses and immunohistochemistry reveal that the hypothalamus and associated regions express angiotensin-converting enzyme 2 and transmembrane proteinase, serine 2, which mediate SARS-CoV-2 cellular entry, in correlation with genes or pathways involved in physiological functions or viral pathogenesis. A post-mortem patient brain shows viral invasion and replication in both the olfactory bulb and the hypothalamus, while animal studies indicate that sex hormones and metabolic diseases influence this susceptibility. Main textSARS-CoV-2 infection is increasingly associated with a wide range of neurological symptomsheadaches, dizziness, nausea, loss of consciousness, seizures, encephalitis etc., as well as anosmia or ageusia -in the majority of patients (1,2). Additionally, many COVID-19 patients with severe disease do not respond well to artificial ventilation or display "silent hypoxia" (3), suggesting an extrapulmonary component to respiratory dysfunction, and cardiorespiratory function and fluid homeostasis are themselves subject to central nervous system (CNS) control. However, despite emerging reports of the post-mortem detection of the virus in the cerebrospinal fluid (CSF) (see for example (4)) or brain parenchyma of patients (5), little is known about how and under what circumstances SARS-CoV-2 infects the brain.While the possibility of CNS infection has been largely underestimated due to the common view that angiotensin converting enzyme 2 (ACE2), the only confirmed cellular receptor for SARS-CoV-2 so far (6), is absent or expressed only at very low levels in the brain (7,8), and that too exclusively in vascular cells (He et al., bioRxiv 2020; doi: https://doi.org/10.1101.088500) the majority of these studies have focused on the cerebral cortex, ignoring the fact that other regions such as the hypothalamus, are rich in ACE2 (9). Intriguingly, most major risk factors for severe COVID-19 (male sex, age, obesity, hypertension, diabetes); reviewed by (10,11); could be mediated by normal or dysfunctional hypothalamic neural networks that regulate a variety of physiological processes: sexual differentiation and gonadal hormone production, energy homeostasis, fluid homeostasis/osmoregulation and even ageing (12)(13)(14). The hypothalamus is also directly linked to other parts of the CNS involved in functions affected in COVID-19 patients, including brainstem nuclei that control fluid homeostasis, cardiac function and respiration, as well as regions implicated in the perception or integration of odor and taste (12,(14)(15)(16)(17)(18).Here, we inves...

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Section: Discussionmentioning

confidence: 99%

The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis

Nampoothiri

Sauvé

Ternier

et al. 2020

Preprint

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“…To cover the main tissues and taste receptors involved in this regulatory pathway, we have had to leave out some details that are covered in recent, more specialised articles focusing on extra-oral bitter 21 or sweet taste receptors, 22 nutrient sensing chemoreceptors, 25 specific physiological conditions 26,27 or selected tissues (eg, respiratory epithelium 28 ).…”

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confidence: 99%

A role for taste receptors in (neuro)endocrinology?

Behrens

Meyerhof

2019

J Neuroendocrinology

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The sense of taste is positioned at the forefront when it comes to the interaction of our body with foodborne chemicals. However, the role of our taste system, and in particular its associated taste receptors, is not limited to driving food preferences leading to ingestion or rejection before other organs take over responsibility for nutrient digestion, absorption and metabolic regulation. Taste sensory elements do much more. On the one hand, extra‐oral taste receptors from the brain to the gut continue to sense nutrients and noxious substances after ingestion and, on the other hand, the nutritional state feeds back on the taste system. This intricate regulatory network is orchestrated by endocrine factors that are secreted in response to taste receptor signalling and, in turn regulate the taste receptor cells themselves. The present review summarises current knowledge on the endocrine regulation of the taste perceptual system and the release of hunger/satiety regulating factors by gastrointestinal taste receptors. Furthermore, the regulation of blood glucose levels via the activation of pancreatic sweet taste receptors and subsequent insulin secretion, as well as the influence of bitter compounds on thyroid hormone release, is addressed. Finally, the central effects of tastants are discussed briefly.

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“…Además, los receptores del gusto acoplados a proteína G (GPCR) para sustancias amargas o dulces se han descrito también en otros tejidos como en vías respiratorias, vía digestiva, colon, testículos y cerebro. [1][2][3][4][5][6] Hoy sabemos que el gusto sólo es una parte de la responsabilidad de estos receptores. Receptores amargos y dulces se consideran quimiosensoriales en muchos tejidos.…”

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“…Receptores amargos y dulces se consideran quimiosensoriales en muchos tejidos. [1][2][3][4][5][6][7][8] Estos receptores extraorales no median el gusto per se, ya que no se unen a vías de percepción neural. La vía respiratoria superior (nariz y senos paranasales) posee receptores amargos y dulces en diferentes tipos celulares influyendo en la respuesta innata de nuestro organismo.…”

unclassified

“…En la vía respiratoria alertan a la célula de patógenos que pueden ocasionar daño, constituyéndose en primera línea de defensa rápida del sistema inmune innato. [1][2][3][4][5] En la lengua estos receptores alertan al cerebro de la presencia de diferentes nutrientes, toxinas y otros químicos que contribuyen al sabor de lo que ingerimos. El sabor constituye una sensación compleja de gusto, olfato, sensación en boca (textura) y algunas veces dolor como en el caso de alimentos condimentados o picantes que contienen capsaicina o alil-isotiocianato que activan a las neuronas sensibles a dolor.…”

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Receptores del gusto en la vía respiratoria. Su importancia en homeostasis nasosinusal

Sacre-Hazouri¹,

Sacre²

2019

Alergia, Asma E Inmunología Pediátricas

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Este artículo puede ser consultado en versión completa en http://www.medigraphic.com/alergia/ Receptores del gusto en la vía respiratoria. Su importancia en homeostasis nasosinusal José Antonio Sacre-Hazouri,* Lauralicia Sacre** RESUMEN El sistema inmune actúa como un sistema sensorial detectando patógenos invasores. Evidencia reciente sugiere que el sistema inmune y el sistema del gusto utilizan algunos de los mismos receptores quimiosensoriales, la familia 2 de los receptores del gusto amargos (T2R). T2R son receptores acoplados a la proteína G originalmente identificados en las células tipo 2 del gusto en la lengua; sin embargo, la expresión de éstos se sabe se extienden a múltiples órganos y sistemas, incluyendo la vía respiratoria. Estudios básicos y clínicos han demostrado que estos T2Rs son parte de una vía de reconocimiento de patógenos en la vía respiratoria y regulan respuestas innatas múltiples tanto en ratones como en humanos. Se ha encontrado que la isoforma T2R38 (familia 2 del receptor del gusto isoforma 38), la cual se expresa en los cilios móviles que se encuentran en la nariz y senos paranasales, se relaciona de manera importante a la inmunidad innata nasosinusal, a la respuesta a infecciones respiratorias superiores y a la rinosinusitis crónica. Esto nos abre un camino potencial de entender mejor estas patologías muy frecuentes. Palabras clave:Receptores del gusto, receptores T2R, receptores T2R38, inmunidad innata en la vía respiratoria superior, rinosinusitis crónica, células quimiosensoriales solitarias. AbstrAct the immune system acts as a sensory system to detect invading pathogens. recent evidence suggests that the immune and taste systems utilize some of the same chemosensory receptors, namely bitter taste receptors of the taste receptor family 2 (T2R). T2Rs are G-protein coupled receptors originally identified in type 2 taste receptor cells of the tongue, but expression of these t2rs is now known to extend to multiple organ systems, including the airway. basic science and clinical studies are establishing t2rs as part of a novel pathogen detection network in the airway, they are expressed in a variety of airway cell types and regulate multiple innate immune responses in both mice and humans. the t2r isoform, taste receptor family 2 isoform 38 protein (t2r38), which is expressed in motile cilia lining the sinonasal cavity (nose and sinuses), has recently been linked with sinonasal innate immunity, upper respiratory infection and chronic rhinosinusitis (crs) demonstrating their importance into human disease and these very frequent diseases.

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Role of Taste Receptors as Sentinels of Innate Immunity in the Upper Airway

Cited by 27 publications

References 78 publications

The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis

The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis

A role for taste receptors in (neuro)endocrinology?

Receptores del gusto en la vía respiratoria. Su importancia en homeostasis nasosinusal

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