Bitter receptor TAS2R138 facilitates lipid droplet degradation in neutrophils during Pseudomonas aeruginosa infection.
Bitter receptor TAS2R138 facilitates lipid droplet degradation in neutrophils during Pseudomonas aeruginosa infection.
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DOI：
10.1038/s41392-021-00602-7
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发表时间：
2021-06-04
影响因子：
39.3
通讯作者：
Wu M
中科院分区：
文献类型：
--
作者：
Pu Q;Guo K;Lin P;Wang Z;Qin S;Gao P;Combs C;Khan N;Xia Z;Wu M
苦味受体主要用于感知味觉，但也可能具有其他功能，例如由于它们对外来物体的敏捷反应而检测致病生物体。小鼠味觉受体2型成员138（TAS 2 R138）是G蛋白偶联苦味受体家族的成员，其不仅存在于舌和鼻腔中，而且广泛分布于其他器官，如呼吸道、肠道和肺。尽管其功能多样，但TAS 2 R138在宿主防御细菌感染中的作用在很大程度上是未知的。在这里，我们发现TAS 2 R138通过与PPARG（过氧化物酶体增殖物激活受体γ）拮抗剂N-（3-氧代十二烷酰基）-l-高丝氨酸内酯（阿勒-12）竞争性结合促进铜绿假单胞菌感染期间中性粒细胞中脂滴（LD）的降解，而PPARG拮抗剂恰好是该细菌（铜绿假单胞菌）产生的毒力结合信号。释放的PPARG然后从细胞核迁移到细胞质，以通过结合PLIN 2（周脂蛋白-2）加速LD的降解。随后，TAS 2 R138-阿勒-12复合物靶向LD以增强其降解，从而促进中性粒细胞中阿勒-12的清除，以维持局部环境的稳态。这些发现揭示了TAS 2 R138在嗜酸性粒细胞介导的针对铜绿假单胞菌感染的宿主免疫中的关键作用。
Bitter receptors function primarily in sensing taste, but may also have other functions, such as detecting pathogenic organisms due to their agile response to foreign objects. The mouse taste receptor type-2 member 138 (TAS2R138) is a member of the G-protein-coupled bitter receptor family, which is not only found in the tongue and nasal cavity, but also widely distributed in other organs, such as the respiratory tract, gut, and lungs. Despite its diverse functions, the role of TAS2R138 in host defense against bacterial infection is largely unknown. Here, we show that TAS2R138 facilitates the degradation of lipid droplets (LDs) in neutrophils during Pseudomonas aeruginosa infection through competitive binding with PPARG (peroxisome proliferator-activated receptor gamma) antagonist: N-(3-oxododecanoyl)-l-homoserine lactone (AHL-12), which coincidently is a virulence-bound signal produced by this bacterium (P. aeruginosa). The released PPARG then migrates from nuclei to the cytoplasm to accelerate the degradation of LDs by binding PLIN2 (perilipin-2). Subsequently, the TAS2R138–AHL-12 complex targets LDs to augment their degradation, and thereby facilitating the clearance of AHL-12 in neutrophils to maintain homeostasis in the local environment. These findings reveal a crucial role for TAS2R138 in neutrophil-mediated host immunity against P. aeruginosa infection.
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影响因子：
39.3
作者：
Li R;Fang L;Pu Q;Lin P;Hoggarth A;Huang H;Li X;Li G;Wu M
通讯作者：
Wu M
影响因子：
2.9
作者：
Boughter JD Jr;Raghow S;Nelson TM;Munger SD
通讯作者：
Munger SD
影响因子：
4
作者：
Grassin-Delyle, Stanislas;Salvator, Helene;Devillier, Philippe
通讯作者：
Devillier, Philippe
影响因子：
37.8
作者：
Goldberg IJ;Reue K;Abumrad NA;Bickel PE;Cohen S;Fisher EA;Galis ZS;Granneman JG;Lewandowski ED;Murphy R;Olive M;Schaffer JE;Schwartz-Longacre L;Shulman GI;Walther TC;Chen J
通讯作者：
Chen J
影响因子：
5.9
作者：
Choi, Jeong-Hwa
通讯作者：
Choi, Jeong-Hwa