Bitter taste receptor T2R14 detects quorum sensing molecules from cariogenic Streptococcus mutans and mediates innate immune responses in gingival epithelial cells

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dc.contributor.authorMedapati, Manoj Reddy
dc.contributor.authorSingh, Nisha
dc.contributor.authorBhagirath, Anjali Yadav
dc.contributor.authorDuan, Kangmin
dc.contributor.authorTriggs-Raine, Barbara
dc.contributor.authorBatista, Eraldo Jr
dc.contributor.authorChelikani, Prashen
dc.date.accessioned2021-02-16T22:35:01Z
dc.date.available2021-02-16T22:35:01Z
dc.date.issued2021
dc.date.submitted2021-01-11T23:33:51Zen_US
dc.description.abstractHost-pathogen interactions play an important role in defining the outcome of a disease. Recent studies have shown bacterial quorum sensing molecules (QSM) can interact with host cell membrane proteins, mainly G protein-coupled receptors (GPCRs), and induce innate immune responses. However, few studies have examined QSM-GPCR interactions and their influence on oral innate immune responses. In this study, we examined the role of bitter taste receptor T2R14 in sensing competence stimulating peptides (CSPs) secreted by cariogenic bacterium Streptococcus mutans and in mediating innate immune responses in gingival epithelial cells (GECs). Transcriptomic and western blot analyses identify T2R14 to be highly expressed in GECs. Our data shows that only CSP-1 from S. mutans induces robust intracellular calcium mobilization compared to CSP-2 and CSP-3. By using CRISPR-Cas9, we demonstrate that CSP-1 induced calcium signaling and secretion of cytokines CXCL-8/IL-8, TNF-α and IL-6 is mediated through T2R14 in GECs. Interestingly, the NF-kB signaling activated by CSP-1 in GECs was independent of T2R14. CSP-1 primed GECs attracted differentiated HL-60 immune cells (dHL-60) and this effect was abolished in T2R14 knock down GECs and also in cells primed with T2R14 antagonist 6-Methoxyflavone (6-MF). Our findings identify S. mutans CSP-1 as a peptide ligand for the T2R family. Our study establishes a novel host-pathogen interaction between cariogenic S. mutans CSP-1 and T2R14 in GECs leading to an innate immune response. Collectively, these findings suggest T2Rs as potential therapeutic targets to modulate innate immune responses upon oral bacterial infections.en_US
dc.description.sponsorshipThis work was supported by Discovery grants (RGPIN-2014-04099 and RGPIN-2020-05670) from the Natural Sciences and Engineering Research Council of Canada (NSERC) and operating grant (491120) from the Canadian Institute of Health Research (CIHR)en_US
dc.identifier.urihttp://hdl.handle.net/1993/35321
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectGingival epithelial cell (GEC), Bitter taste receptor 14 (T2R14), S. mutans,Competence stimulating peptide (CSP), Host-pathogen interaction, Innate immune responses.en_US
dc.titleBitter taste receptor T2R14 detects quorum sensing molecules from cariogenic Streptococcus mutans and mediates innate immune responses in gingival epithelial cellsen_US
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