Bitter Taste Receptor T2R14 Modulates Gram-Positive Bacterial Internalization and Survival in Gingival Epithelial Cells.
Bitter Taste Receptor T2R14 Modulates Gram-Positive Bacterial Internalization and Survival in Gingival Epithelial Cells.
复制标题
苦味受体T2R14调节牙龈上皮细胞中革兰氏阳性细菌的内化和存活。
DOI：
10.3390/ijms22189920
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发表时间：
2021-09-14
影响因子：
5.6
通讯作者：
Chelikani P
中科院分区：
文献类型：
--
作者：
Medapati MR;Bhagirath AY;Singh N;Schroth RJ;Bhullar RP;Duan K;Chelikani P
苦味受体（T2Rs）已成为宿主-病原体相互作用的关键参与者和口腔先天免疫的重要调节剂。此前，我们报道了T2R14在牙龈上皮细胞（GECs）中表达，并与致龋变形链球菌分泌的能力刺激肽（CSPs）相互作用。T2R14对革兰氏阳性菌的先天免疫反应和生理作用的潜在机制尚不清楚。在这项研究中，我们研究了T2R14在革兰氏阳性细菌，即金黄色葡萄球菌和变形链球菌的内化和生长抑制作用中的作用。我们利用CRISPR-Cas9 T2R14敲低（KD）基因作为研究模型来解决这些关键的生理机制。我们的数据显示，金黄色葡萄球菌的内化显著减少，而变形葡萄球菌的内化不受基因敲除T2R14的影响。令人惊讶的是，用变形链球菌CSP-1引物的gec对金黄色葡萄球菌的生长有抑制作用，但对变形链球菌没有抑制作用。金黄色葡萄球菌感染的gec诱导t2r14依赖性人β-防御素-2 （hBD-2）分泌；然而，变形链球菌感染的gec不诱导hBD-2分泌，但诱导依赖于T2R14的IL-8分泌。有趣的是，我们的研究结果表明，T2R14 KD影响gec中的细胞骨架重组，从而抑制金黄色葡萄球菌的内化。我们的研究强调了T2R14在影响口腔对革兰氏阳性细菌的生理反应中的独特机制和直接作用。
Bitter-taste receptors (T2Rs) have emerged as key players in host–pathogen interactions and important modulators of oral innate immunity. Previously, we reported that T2R14 is expressed in gingival epithelial cells (GECs) and interacts with competence stimulating peptides (CSPs) secreted by the cariogenic Streptococcus mutans. The underlying mechanisms of the innate immune responses and physiological effects of T2R14 on Gram-positive bacteria are not well characterized. In this study, we examined the role of T2R14 in internalization and growth inhibitory effects on Gram-positive bacteria, namely Staphylococcus aureus and S. mutans. We utilized CRISPR-Cas9 T2R14 knockdown (KD) GECs as the study model to address these key physiological mechanisms. Our data reveal that the internalization of S. aureus is significantly decreased, while the internalization of S. mutans remains unaffected upon knockdown of T2R14 in GECs. Surprisingly, GECs primed with S. mutans CSP-1 resulted in an inhibition of growth for S. aureus, but not for S. mutans. The GECs infected with S. aureus induced T2R14-dependent human β-defensin-2 (hBD-2) secretion; however, S. mutans–infected GECs did not induce hBD-2 secretion, but induced T2R14 dependent IL-8 secretion. Interestingly, our results show that T2R14 KD affects the cytoskeletal reorganization in GECs, thereby inhibiting S. aureus internalization. Our study highlights the distinct mechanisms and a direct role of T2R14 in influencing physiological responses to Gram-positive bacteria in the oral cavity.
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影响因子：
5.2
作者：
de Jesus VC;Khan MW;Mittermuller BA;Duan K;Hu P;Schroth RJ;Chelikani P
通讯作者：
Chelikani P
影响因子：
15.9
作者：
Lee, Robert J.;Xiong, Guoxiang;Cohen, Noam A.
通讯作者：
Cohen, Noam A.
影响因子：
64.5
作者：
Adler, E;Hoon, MA;Zuker, CS
通讯作者：
Zuker, CS
影响因子：
8
作者：
Gopallawa, Indiwari;Freund, Jenna R.;Lee, Robert J.
通讯作者：
Lee, Robert J.
影响因子：
4.8
作者：
Medapati, Manoj Reddy;Singh, Nisha;Chelikani, Prashen
通讯作者：
Chelikani, Prashen