In Vivo Biofilm Formation, Gram‐Negative Infections and <scp>TAS</scp>2<scp>R</scp>38 Polymorphisms in <scp>CRS</scp>w <scp>NP</scp> Patients

Cantone, Elena; Negri, Rossella; Roscetto, Emanuela; Grassia, Rossella; Catania, Maria Rosaria; Capasso, Pasquale; Maffei, Marianna; Soriano, Amata Amy; Leone, Carlo Antonio; Iengo, Maurizio; Greco, Luigi

doi:10.1002/lary.27175

Cited by 36 publications

(46 citation statements)

References 44 publications

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“…1 (b and c) and 2e). Together, these results suggest that several T2Rs expressed in the airway can detect bacterial quinolones, including T2R38, which has been implicated in chronic rhinosinusitis (12,23,(25)(26)(27)(28)(29)71).…”

Section: Pqs and Hhq Activate T2r-dependent Ca 2؉ Signals In A Heteromentioning

confidence: 74%

“…The relevance of T2R38 to immunity is supported by clinical data linking polymorphisms in the TAS2R38 gene to sinonasal disease (16,21). Patients homozygous for the AVI TAS2R38 polymorphism, which results in nonfunctional T2R38 protein (22), are more susceptible to Gram-negative bacterial infection (12), have higher levels of sinonasal bacteria (23,24) and biofilms (25), are at higher risk for chronic rhinosinusitis (26 -29), and may have worse outcomes after endoscopic sinus surgery (30) compared with patients homozygous for the functional (PAV) allele of TAS2R38.…”

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confidence: 98%

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Activation of airway epithelial bitter taste receptors by Pseudomonas aeruginosa quinolones modulates calcium, cyclic-AMP, and nitric oxide signaling

Freund

Mansfield

Doghramji

et al. 2018

Journal of Biological Chemistry

100

158

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Bitter taste receptors (taste family 2 bitter receptor proteins; T2Rs), discovered in many tissues outside the tongue, have recently become potential therapeutic targets. We have shown previously that airway epithelial cells express several T2Rs that activate innate immune responses that may be important for treatment of airway diseases such as chronic rhinosinusitis. It is imperative to more clearly understand what compounds activate airway T2Rs as well as their full range of functions. T2R isoforms in airway motile cilia (T2R4, -14, -16, and -38) produce bactericidal levels of nitric oxide (NO) that also increase ciliary beating, promoting clearance of mucus and trapped pathogens. Bacterial quorum-sensing acyl-homoserine lactones activate T2Rs and stimulate these responses in primary airway cells. Quinolones are another type of quorum-sensing molecule used by To elucidate whether bacterial quinolones activate airway T2Rs, we analyzed calcium, cAMP, and NO dynamics using a combination of fluorescent indicator dyes and FRET-based protein biosensors. T2R-transfected HEK293T cells, several lung epithelial cell lines, and primary sinonasal cells grown and differentiated at the air-liquid interface were tested with 2-heptyl-3-hydroxy-4-quinolone (known as quinolone signal; PQS), 2,4-dihydroxyquinolone, and 4-hydroxy-2-heptylquinolone (HHQ). In HEK293T cells, PQS activated T2R4, -16, and -38, whereas HHQ activated T2R14. 2,4-Dihydroxyquinolone had no effect. PQS and HHQ increased calcium and decreased both baseline and stimulated cAMP levels in cultured and primary airway cells. In primary cells, PQS and HHQ activated levels of NO synthesis previously shown to be bactericidal. This study suggests that airway T2R-mediated immune responses are activated by bacterial quinolones as well as acyl-homoserine lactones.

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Section: Pqs and Hhq Activate T2r-dependent Ca 2؉ Signals In A Heteromentioning

confidence: 74%

mentioning

confidence: 98%

Activation of airway epithelial bitter taste receptors by Pseudomonas aeruginosa quinolones modulates calcium, cyclic-AMP, and nitric oxide signaling

Freund

Mansfield

Doghramji

et al. 2018

Journal of Biological Chemistry

100

158

View full text Add to dashboard Cite

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“…Additionally, AVI homozygotes with CRS are more likely to require surgical intervention for medically recalcitrant sinusitis. 55 , 56 , 57 , 58 , 59 , 60 Furthermore, PAV/PAV patients with non-polypoid CRS have better quality of life outcomes 6 months after sinus surgery when compared to heterozygotes and AVI homozygous patients. More recently, genome-wide association tests have identified other less well-studied bitter and sweet receptor genes that are associated with CRS including TAS2R13 and TAS2R49 suggesting that we have only begun to scratch the surface in our understanding of how taste related genes play a role in the pathogenesis of CRS.…”

Section: Introductionmentioning

confidence: 97%

The role of bitter and sweet taste receptors in upper airway innate immunity: Recent advances and future directions

Maina

Workman

Cohen

2018

World j. otorhinolaryngol.-head neck surg.

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Bitter (T2R) and sweet (T1R) taste receptors have been implicated in sinonasal innate immunity and in the pathophysiology of chronic rhinosinusitis (CRS). Taste receptors are expressed on several sinonasal cell types including ciliated epithelial cells and solitary chemosensory cells. Bitter agonists released by pathogenic microbes elicit a T2R dependent signaling cascade which induces the release of bactericidal nitric oxide, increases mucociliary clearance, and promotes secretion of antimicrobial peptides. Genetic variation conferred by polymorphisms in T2R related genes is associated with differential CRS susceptibility, symptomatology and post-treatment outcomes. More recently, based on our understanding of T1R and T2R function, investigators have discovered novel potential therapeutics in T2R agonists and T1R antagonists. This review will discuss bitter and sweet taste receptor function in sinonasal immunity, explore the emerging diagnostic and therapeutic implications stemming from the most recent findings, and suggest directions for future research.

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“…A single study that included only 53 patients with chronic rhinosinusitis and 39 healthy controls did not find associations between TAS2R38 genotypes and sinonasal disease 33 . Finally, a study by Cantone et al 34 on 100 subjects confirmed the inverse correlation between TAS2R38 functionality and the risk of developing sinonasal infections caused by gram-negative bacteria. The present study, which included 210 patients with CF and 95 control subjects, confirms that CF patients with both functional alleles of TAS2R38 have a significantly reduced risk of developing to the most severe phase of sinonasal disease, i.e., NP requiring surgery.…”

Section: Discussionmentioning

confidence: 78%

TAS2R38 is a novel modifier gene in patients with cystic fibrosis

Castaldo

Cernera

Iacotucci

et al. 2020

Sci Rep

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The clinical manifestation of cystic fibrosis (CF) is heterogeneous also in patients with the same cystic fibrosis transmembrane regulator (CFTR) genotype and in affected sibling pairs. Other genes, inherited independently of CFTR, may modulate the clinical manifestation and complications of patients with CF, including the severity of chronic sinonasal disease and the occurrence of chronic Pseudomonas aeruginosa colonization. The T2R38 gene encodes a taste receptor and recently its functionality was related to the occurrence of sinonasal diseases and upper respiratory infections. We assessed the T2R38 genotype in 210 patients with CF and in 95 controls, relating the genotype to the severity of sinonasal disease and to the occurrence of P. aeruginosa pulmonary colonization. The frequency of the PAV allele i.e., the allele associated with the high functionality of the T2R38 protein, was significantly lower in i) CF patients with nasal polyposis requiring surgery, especially in patients who developed the complication before 14 years of age; and ii) in CF patients with chronic pulmonary colonization by P. aeruginosa, especially in patients who were colonized before 14 years of age, than in control subjects. These data suggest a role for T2R38 as a novel modifier gene of sinonasal disease severity and of pulmonary P. aeruginosa colonization in patients with CF.

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In Vivo Biofilm Formation, Gram‐Negative Infections and TAS2R38 Polymorphisms in CRSw NP Patients

Abstract: 2b. Laryngoscope, 128:E339-E345, 2018.

Cited by 36 publications

References 44 publications

Activation of airway epithelial bitter taste receptors by Pseudomonas aeruginosa quinolones modulates calcium, cyclic-AMP, and nitric oxide signaling

Activation of airway epithelial bitter taste receptors by Pseudomonas aeruginosa quinolones modulates calcium, cyclic-AMP, and nitric oxide signaling

The role of bitter and sweet taste receptors in upper airway innate immunity: Recent advances and future directions

TAS2R38 is a novel modifier gene in patients with cystic fibrosis

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