T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection
T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection
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DOI：
10.1172/jci64240
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发表时间：
2012-11-01
影响因子：
15.9
通讯作者：
Cohen, Noam A.
中科院分区：
文献类型：
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作者：
Lee, Robert J.;Xiong, Guoxiang;Cohen, Noam A.
天生的和适应性的防御机制保护呼吸系统免受微生物的攻击。在这里，我们提出了苦味受体T2R38调节人类上呼吸道粘膜固有防御的证据。利用免疫荧光和活细胞成像技术，我们证明了T2R38在人的上呼吸道上皮细胞中表达，并在铜绿假单胞菌和其他革兰氏阴性细菌分泌的酰基高丝氨酸内酯群体感应分子的响应下被激活。受体激活调节钙依赖的NO的产生，从而刺激粘液纤毛清除和直接的抗菌作用。此外，TAS2R38基因的常见多态与上呼吸道细胞清除和杀灭细菌的能力存在显著差异。TAS2R38基因与人类鼻腔革兰氏阴性细菌感染相关。这些数据表明，T2R38是先天防御的上呼吸道哨兵，遗传变异导致了呼吸道感染易感性的个体差异。
Innate and adaptive defense mechanisms protect the respiratory system from attack by microbes. Here, we present evidence that the bitter taste receptor T2R38 regulates the mucosal innate defense of the human upper airway. Utilizing immunofluorescent and live cell imaging techniques in polarized primary human sinonasal cells, we demonstrate that T2R38 is expressed in human upper respiratory epithelium and is activated in response to acyl-homoserine lactone quorum-sensing molecules secreted by Pseudomonas aeruginosa and other gram-negative bacteria. Receptor activation regulates calcium-dependent NO production, resulting in stimulation of mucociliary clearance and direct antibacterial effects. Moreover, common polymorphisms of the TAS2R38 gene were linked to significant differences in the ability of upper respiratory cells to clear and kill bacteria. Lastly, TAS2R38 genotype correlated with human sinonasal gram-negative bacterial infection. These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation contributes to individual differences in susceptibility to respiratory infection.