Cohen Noam A
Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.
Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, U.S.A.
Laryngoscope. 2017 Jan;127(1):44-51. doi: 10.1002/lary.26198. Epub 2016 Sep 21.
Chronic rhinosinusitis (CRS) refractory to therapeutic intervention may involve a particularly resistant infection known as a bacterial biofilm. Critical to biofilm formation is the microbial process of quorum sensing whereby microbes secrete factors that regulate the expression of microbial genes involved in biofilm formation, persistence, and virulence. Here, we review recent work demonstrating that the bitter taste receptor T2R38, expressed on the apical surface of the sinonasal epithelium, serves a sentinel role in eavesdropping on microbial quorum-sensing communications and regulates localized innate biocidal defenses. Furthermore, studies investigating whether cilia are necessary for T2R38 expression and function in the upper airway are presented.
Primary human sinonasal air-liquid interface cultures were used to elucidate cellular pathways responsive to quorum-sensing molecules, whereas clinical studies investigated the contribution of T2R38 polymorphisms to recalcitrant chronic rhinosinusitis.
T2R38 is stimulated by acyl-homoserine lactones, gram-negative quorum-sensing molecules, and subsequently activates nitric oxide-dependent innate immune responses. The formation of mature cilia is necessary for T2R38 expression and function, and polymorphisms that underlie T2R38 functionality appear to be involved in susceptibility to upper respiratory infection and recalcitrant CRS.
Taste receptors are emerging as critical components of early-phase respiratory innate immunity, detecting molecules used by microbes to communicate and stimulating localized host defenses. Genetic polymorphisms are very common within the taste receptors, and recent linkage studies have demonstrated associations of taste receptor genetics with CRS. Lastly, ciliogenesis, which is often impacted in CRS, is critical for the functional expression of T2R38.
N/A. Laryngoscope, 127:44-51, 2017.
对治疗干预难治的慢性鼻-鼻窦炎（CRS）可能涉及一种特别耐药的感染，即细菌生物膜。群体感应是生物膜形成的关键微生物过程，在此过程中，微生物分泌调节参与生物膜形成、持续存在和毒力的微生物基因表达的因子。在此，我们综述近期的研究工作，这些研究表明，表达于鼻窦上皮顶端表面的苦味受体T2R38在监听微生物群体感应通讯中起哨兵作用，并调节局部先天性杀菌防御。此外，还介绍了关于纤毛对T2R38在上呼吸道的表达和功能是否必要的研究。
使用原代人鼻窦气液界面培养物来阐明对群体感应分子有反应的细胞途径，而临床研究则调查T2R38基因多态性对顽固性慢性鼻-鼻窦炎的作用。
T2R38受酰基高丝氨酸内酯（革兰氏阴性菌群体感应分子）刺激，随后激活一氧化氮依赖性先天性免疫反应。成熟纤毛的形成对T2R38的表达和功能是必要的，构成T2R38功能基础的基因多态性似乎与上呼吸道感染和顽固性CRS的易感性有关。
味觉受体正成为早期呼吸道先天性免疫的关键组成部分，可以检测微生物用于通讯的分子并刺激局部宿主防御。味觉受体中的基因多态性非常普遍，最近的连锁研究已证明味觉受体遗传学与CRS有关。最后，在CRS中常受影响的纤毛发生对于T2R38的功能表达至关重要。
无。《喉镜》，2017年，第127卷，第44 - 51页。
