Bitter taste receptor T2R14-Gαi coupling mediates innate immune responses to microbial quorum sensing molecules in cystic fibrosis

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2024-10-30 DOI:10.1016/j.isci.2024.111286

Nisha Singh , Ryan H. Cunnington , Anjali Bhagirath , Ankita Vaishampayan , Mohd Wasif Khan , Tejas Gupte , Kangmin Duan , Abdelilah S. Gounni , Shyamala Dakshisnamurti , John W. Hanrahan , Prashen Chelikani

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Abstract

Cystic fibrosis (CF) is an autosomal recessive disease characterized by microbial infection and progressive decline in lung function, leading to significant morbidity and mortality. The bitter taste receptor T2R14 is a chemosensory receptor that is significantly expressed in airways. Using a combination of cell-based assays and T2R14 knockdown in bronchial epithelial cells from CF and non-CF individuals, we observed that T2R14 plays a crucial role in the detection of bacterial and fungal signals and enhances host innate immune responses. Expression of Gαi protein is enhanced in CF bronchial epithelial cells and T2R14-Gαi specific signaling leads to increased calcium mobilization. Knockdown of T2R14 leads to reduced innate immune activation by bacterial strains deficient in quorum sensing. The results demonstrate that T2R14 helps protect against microbial infection and thus may play an important role in the innate immune defense of the CF airway epithelium.

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苦味受体 T2R14-Gαi 偶联介导囊性纤维化患者对微生物法定量传感分子的先天性免疫反应

囊性纤维化（CF）是一种常染色体隐性遗传病，以微生物感染和肺功能进行性下降为特征，导致严重的发病率和死亡率。苦味受体 T2R14 是一种化学感觉受体，在气道中显著表达。通过细胞检测和 T2R14 在 CF 和非 CF 患者支气管上皮细胞中的敲除相结合的方法，我们观察到 T2R14 在检测细菌和真菌信号以及增强宿主先天性免疫反应中起着至关重要的作用。Gαi蛋白在CF支气管上皮细胞中的表达增强，T2R14-Gαi特异性信号转导导致钙动员增加。敲除 T2R14 会导致缺乏法定量感应的细菌菌株对先天性免疫的激活降低。研究结果表明，T2R14有助于抵御微生物感染，因此可能在CF气道上皮细胞的先天性免疫防御中发挥重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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