{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T04:42:02Z","timestamp":1759984922289,"version":"build-2065373602"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Bitter taste receptors (TAS2Rs), initially identified for chemosensory roles in the tongue, are expressed in extraoral tissues, including the airways. However, to date, it remains unclear whether bitter signaling is associated with susceptibility to bacterial infection in the lower airways and whether bitter signaling actually participates in the immune response in lung infection has yet to be genetically established. Here, we investigated the role of TAS2R signaling in <jats:italic>Staphylococcus aureus<\/jats:italic>-induced murine pneumonia via wild-type (WT) and several mutants (mTas2r104<jats:sup>-\/-<\/jats:sup>\/105<jats:sup>-\/-<\/jats:sup>, mTas2r105<jats:sup>-\/-<\/jats:sup>\/114<jats:sup>-\/-<\/jats:sup>, mTas2r104<jats:sup>-\/-<\/jats:sup>\/105<jats:sup>-\/-<\/jats:sup>\/114<jats:sup>-\/-<\/jats:sup>, Gnat3<jats:sup>-\/-<\/jats:sup> and Gnat3<jats:sup>-\/\u2013<\/jats:sup>mTas2r104<jats:sup>-\/-<\/jats:sup>\/105<jats:sup>-\/-<\/jats:sup>) mice. Genetic disruption of TAS2Rs altered compensatory expression of other bitter receptors in the trachea and lungs, but did not affect immune cell composition in the lungs or thymus. Bitter receptor-deficient mice exhibited exacerbated pulmonary lesions at day 3 (D3) post-infection. Pulmonary infection significantly upregulated <jats:italic>mTas2r105<\/jats:italic>,<jats:italic>106<\/jats:italic>, <jats:italic>107<\/jats:italic>, <jats:italic>108<\/jats:italic>, <jats:italic>126<\/jats:italic>, <jats:italic>136<\/jats:italic>, <jats:italic>138<\/jats:italic> and <jats:italic>Gnat3<\/jats:italic> in the lung. TAS2R signaling deficiency downregulated the expression of cytokines (e.g., IL-10, MIP-2) and antimicrobial peptides in the lungs and trachea, increased CD68+ macrophages in D3 lung tissues, amplified Ki67+ cell proliferation in alveolar and bronchiolar regions, and even impaired recovery from lung injury by day 14 (D14). Mechanistically, bitter taste pathway disruption dysregulated the mTOR pathway, reduced eNOS expression, and delayed resolution of pneumonia-induced injury. In summary, the current results collectively indicate that bitter taste signaling can modulate innate immune and inflammatory responses during S. aureus-induced lung infection.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1647780","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T04:23:07Z","timestamp":1759983787000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Contribution of the bitter taste signaling pathway to lung inflammation during Staphylococcus aureus-induced pneumonia"],"prefix":"10.3389","volume":"16","author":[{"given":"Ling-Ling","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng-Min","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo-Wen","family":"Niu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lixiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boyin","family":"Qin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00134-14","article-title":"Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management","volume":"28","author":"Tong","year":"2015","journal-title":"Clin Microbiol Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268814000983","article-title":"Community-associated methicillin-resistant Staphylococcus aureus transmission in households of infected cases: a pooled analysis of primary data from three studies across international settings","volume":"143","author":"Knox","year":"2015","journal-title":"Epidemiol Infect"},{"key":"B3","doi-asserted-by":"publisher","first-page":"9710376","DOI":"10.1155\/2022\/9710376","article-title":"Human leukocyte antigen (HLA) system: genetics and association with bacterial and viral infections","volume":"2022","author":"Medhasi","year":"2022","journal-title":"J Immunol Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00183814","article-title":"Myeloid-related protein-14 deficiency promotes inflammation in staphylococcal pneumonia","volume":"46","author":"Achouiti","year":"2015","journal-title":"Eur Respir J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2015.05.008","article-title":"Complex host genetic susceptibility to Staphylococcus aureus infections","volume":"23","author":"Shukla","year":"2015","journal-title":"Trends Microbiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2015.00242","article-title":"Toll-like receptor 9 enhances bacterial clearance and limits lung consolidation in murine pneumonia caused by methicillin resistant Staphylococcus aureus","volume":"22","author":"van der Meer","year":"2016","journal-title":"Mol Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12331","article-title":"Characterization of genetic humanized mice with transgenic HLA DP401 or DRA but deficient in endogenous murine MHC class II genes upon Staphylococcus aureus pneumonia","volume":"6","author":"Li","year":"2023","journal-title":"Anim Model Exp Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/S0092-8674(00)80705-9","article-title":"A novel family of mammalian taste receptors","volume":"100","author":"Adler","year":"2000","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23179677","article-title":"Taste receptors beyond taste buds","volume":"23","author":"Ki","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12357","article-title":"Genetic mutation of Tas2r104\/Tas2r105\/Tas2r114 cluster leads to a loss of taste perception to denatonium benzoate and cucurbitacin B","volume":"7","author":"Niu","year":"2024","journal-title":"Anim Model Exp Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nature05401","article-title":"The receptors and cells for mammalian taste","volume":"444","author":"Chandrashekar","year":"2006","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"crossref","first-page":"e2121513119","DOI":"10.1073\/pnas.2121513119","article-title":"Tas2R activation relaxes airway smooth muscle by release of Galpha(t) targeting on AChR signaling","volume":"119","author":"Zhou","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2237","article-title":"Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction","volume":"16","author":"Deshpande","year":"2010","journal-title":"Nat Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2017.02.002","article-title":"Taste and smell GPCRs in the lung: Evidence for a previously unrecognized widespread chemosensory system","volume":"41","author":"An","year":"2018","journal-title":"Cell Signal"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1126\/science.1173869","article-title":"Motile cilia of human airway epithelia are chemosensory","volume":"325","author":"Shah","year":"2009","journal-title":"Science"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1172\/JCI150951","article-title":"Bitter taste signaling in tracheal epithelial brush cells elicits innate immune responses to bacterial infection","volume":"132","author":"Hollenhorst","year":"2022","journal-title":"J Clin Invest"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-020-03494-y","article-title":"Bitter taste receptors stimulate phagocytosis in human macrophages through calcium, nitric oxide, and cyclic-GMP signaling","volume":"78","author":"Gopallawa","year":"2021","journal-title":"Cell Mol Life Sci"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01267","article-title":"Bitter taste receptors (TAS2Rs) in human lung macrophages: receptor expression and inhibitory effects of TAS2R agonists","volume":"10","author":"Grassin-Delyle","year":"2019","journal-title":"Front Physiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s41392-021-00602-7","article-title":"Bitter receptor TAS2R138 facilitates lipid droplet degradation in neutrophils during Pseudomonas aeruginosa infection","volume":"6","author":"Pu","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.02.029","article-title":"Bitter taste receptor (TAS2R) agonists inhibit IgE-dependent mast cell activation","volume":"134","author":"Ekoff","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.2A0714-331RR","article-title":"Class I odorant receptors, TAS1R and TAS2R taste receptors, are markers for subpopulations of circulating leukocytes","volume":"97","author":"Malki","year":"2015","journal-title":"J Leukoc Biol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/nu11092017","article-title":"Taste receptors in upper airway innate immunity","volume":"11","author":"Carey","year":"2019","journal-title":"Nutrients"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.001005","article-title":"Activation of airway epithelial bitter taste receptors by Pseudomonas aeruginosa quinolones modulates calcium, cyclic-AMP, and nitric oxide signaling","volume":"293","author":"Freund","year":"2018","journal-title":"J Biol Chem"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12158","article-title":"Generation and expression analysis of BAC humanized mice carrying HLA-DP401 haplotype","volume":"4","author":"Li","year":"2021","journal-title":"Anim Model Exp Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1992.tb02045.x","article-title":"Definition and application of a histopathological scoring scheme for an animal model of acute Mycoplasma pneumoniae pulmonary infection","volume":"36","author":"Cimolai","year":"1992","journal-title":"Microbiol Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"489","DOI":"10.4049\/jimmunol.2000085","article-title":"Hypercapnia suppresses macrophage antiviral activity and increases mortality of influenza A infection via akt1","volume":"205","author":"Casalino-Matsuda","year":"2020","journal-title":"J Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.170316","article-title":"Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus","volume":"9","author":"Casalino-Matsuda","year":"2024","journal-title":"JCI Insight"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gas005","article-title":"Depletion of bitter taste transduction leads to massive spermatid loss in transgenic mice","volume":"18","author":"Li","year":"2012","journal-title":"Mol Hum Reprod"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gat009","article-title":"Taste perception: from the tongue to the testis","volume":"19","author":"Li","year":"2013","journal-title":"Mol Hum Reprod"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30315","article-title":"Genetic deletion of the Tas2r143\/Tas2r135\/Tas2r126 cluster reveals that TAS2Rs may not mediate bitter tastant-induced bronchodilation","volume":"236","author":"Lu","year":"2021","journal-title":"J Cell Physiol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00849","article-title":"Members of bitter taste receptor cluster tas2r143\/tas2r135\/tas2r126 are expressed in the epithelium of murine airways and other non-gustatory tissues","volume":"8","author":"Liu","year":"2017","journal-title":"Front Physiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2015.06.005","article-title":"Cholinergic chemosensory cells of the thymic medulla express the bitter receptor Tas2r131","volume":"29","author":"Soultanova","year":"2015","journal-title":"Int Immunopharmacol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1074\/jbc.R100054200","article-title":"Molecular mechanisms of bitter and sweet taste transduction","volume":"277","author":"Margolskee","year":"2002","journal-title":"J Biol Chem"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2023-0168","article-title":"Anti-Staphylococcus aureus effects of natural antimicrobial peptides and the underlying mechanisms","volume":"19","author":"Chen","year":"2024","journal-title":"Future Microbiol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.6.3609-3617.2005","article-title":"Antimicrobial activity of murine lung cells against Staphylococcus aureus is increased in vitro and in vivo after elafin gene transfer","volume":"73","author":"McMichael","year":"2005","journal-title":"Infect Immun"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1086\/513277","article-title":"Staphylococcus aureus exploits cathelicidin antimicrobial peptides produced during early pneumonia to promote staphylokinase-dependent fibrinolysis","volume":"195","author":"Braff","year":"2007","journal-title":"J Infect Dis"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.VMBF-0006-2015","article-title":"Bacterial evasion of host antimicrobial peptide defenses","volume":"4","author":"Cole","year":"2016","journal-title":"Microbiol Spectr"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e13722","DOI":"10.7554\/eLife.13722","article-title":"The cell proliferation antigen Ki-67 organises heterochromatin","volume":"5","author":"Sobecki","year":"2016","journal-title":"Elife"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.669403","article-title":"AGR3 regulates airway epithelial junctions in patients with frequent exacerbations of COPD","volume":"12","author":"Ye","year":"2021","journal-title":"Front Pharmacol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.80","article-title":"Tight junctions: from simple barriers to multifunctional molecular gates","volume":"17","author":"Zihni","year":"2016","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B41","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.92956.3","article-title":"G protein subunit Ggamma13-mediated signaling pathway is critical to the inflammation resolution and functional recovery of severely injured lungs","volume":"12","author":"Li","year":"2024","journal-title":"Elife"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.726546","article-title":"TAS2R16 activation suppresses LPS-induced cytokine expression in human gingival fibroblasts","volume":"12","author":"Zhou","year":"2021","journal-title":"Front Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.13.0831","article-title":"Cathelicidin and human beta-defensin 2 in bronchoalveolar lavage fluid of children with pulmonary tuberculosis","volume":"18","author":"Cakir","year":"2014","journal-title":"Int J Tuberc Lung Dis"},{"key":"B44","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.tcm.2005.11.004","article-title":"Defective lung vascular development in endothelial nitric oxide synthase-deficient mice","volume":"16","author":"Han","year":"2006","journal-title":"Trends Cardiovasc Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00395.2005","article-title":"Inhaled NO restores lung structure in eNOS-deficient mice recovering from neonatal hypoxia","volume":"291","author":"Balasubramaniam","year":"2006","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e13196","DOI":"10.1111\/acel.13196","article-title":"Vascular dysfunction in aged mice contributes to persistent lung fibrosis","volume":"19","author":"Caporarello","year":"2020","journal-title":"Aging Cell"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.017","article-title":"mTOR signaling in growth control and disease","volume":"149","author":"Laplante","year":"2012","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.004581","article-title":"Mammalian target of rapamycin complex 2 (mTORC2) coordinates pulmonary artery smooth muscle cell metabolism, proliferation, and survival in pulmonary arterial hypertension","volume":"129","author":"Goncharov","year":"2014","journal-title":"Circulation"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2016.03.008","article-title":"Emerging role of mTOR in the response to cancer therapeutics","volume":"2","author":"Ilagan","year":"2016","journal-title":"Trends Cancer"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93203","article-title":"mTOR pathway activation drives lung cell senescence and emphysema","volume":"3","author":"Houssaini","year":"2018","journal-title":"JCI Insight"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1172\/JCI171430","article-title":"Activation of mTOR signaling in adult lung microvascular progenitor cells accelerates lung aging","volume":"133","author":"Mason","year":"2023","journal-title":"J Clin Invest"},{"key":"B52","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3410\/B3-20","article-title":"Taste isn\u2019t just for taste buds anymore","volume":"3","author":"Finger","year":"2011","journal-title":"F1000 Biol Rep"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3390\/cells10112889","article-title":"Taste receptors: the gatekeepers of the airway epithelium","volume":"10","author":"Martens","year":"2021","journal-title":"Cells"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3390\/cells11223638","article-title":"The complex journey of the calcium regulation downstream of TAS2R activation","volume":"11","author":"Talmon","year":"2022","journal-title":"Cells"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43038","article-title":"GPCR signaling inhibits mTORC1 via PKA phosphorylation of Raptor","volume":"8","author":"Jewell","year":"2019","journal-title":"Elife"},{"key":"B56","doi-asserted-by":"crossref","DOI":"10.1152\/ajpcell.00210.2022","article-title":"Rockman HA. G protein-coupled receptor signaling: transducers and effectors","volume":"323","author":"Jiang","year":"2022","journal-title":"Am J Physiol Cell Physiol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26134100","article-title":"Targeting the PI3K\/AKT\/mTOR signaling pathway in lung cancer: an update regarding potential drugs and natural products","volume":"26","author":"Iksen","year":"2021","journal-title":"Molecules"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3390\/cells11091478","article-title":"HSP90 modulates T2R bitter taste receptor nitric oxide production and innate immune responses in human airway epithelial cells and macrophages","volume":"11","author":"Carey","year":"2022","journal-title":"Cells"},{"key":"B59","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1038\/s42003-022-03653-w","article-title":"mTOR contributes to endothelium-dependent vasorelaxation by promoting eNOS expression and preventing eNOS uncoupling","volume":"5","author":"Wang","year":"2022","journal-title":"Commun Biol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1816030116","article-title":"ABL kinase inhibition promotes lung regeneration through expansion of an SCGB1A1+ SPC+ cell population following bacterial pneumonia","volume":"116","author":"Khatri","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1593\/neo.121088","article-title":"E-cadherin controls bronchiolar progenitor cells and onset of preneoplastic lesions in mice","volume":"14","author":"Ceteci","year":"2012","journal-title":"Neoplasia"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1172\/JCI172058","article-title":"Beyond epithelial damage: vascular and endothelial contributions to idiopathic pulmonary fibrosis","volume":"133","author":"May","year":"2023","journal-title":"J Clin Invest"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2018-0101PS","article-title":"The emerging role of neutrophils in repair after acute lung injury","volume":"59","author":"Blazquez-Prieto","year":"2018","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3390\/cells10020436","article-title":"Macrophages in lung injury, repair, and fibrosis","volume":"10","author":"Cheng","year":"2021","journal-title":"Cells"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.629281","article-title":"Critical role of lkb1 in the maintenance of alveolar macrophage self-renewal and immune homeostasis","volume":"12","author":"Wang","year":"2021","journal-title":"Front Immunol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1038\/s41467-023-37099-3","article-title":"Bitter taste cells in the ventricular walls of the murine brain regulate glucose homeostasis","volume":"14","author":"Yu","year":"2023","journal-title":"Nat Commun"},{"key":"B67","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1093\/stmcls\/sxad075","article-title":"Bitter taste receptor agonist denatonium inhibits stemness characteristics in hematopoietic stem\/progenitor cells","volume":"42","author":"Pensato","year":"2024","journal-title":"Stem Cells"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1647780\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T04:23:09Z","timestamp":1759983789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1647780\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,9]]},"references-count":67,"alternative-id":["10.3389\/fimmu.2025.1647780"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1647780","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,9]]},"article-number":"1647780"}}