Abstract

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.

Highlights

  • Taste is one of the most important sensing functions in mammals, among which bitterness is one of the five basic tastes

  • TAS2R138 increases in alveolar macrophages (AMs) and neutrophils during P. aeruginosa infection AMs and neutrophils are among the highest proportions of migratory phagocytic cells in airspaces of the lung during bacterial infection

  • The data showed that Tas2r138 was the most highly expressed receptor in neutrophils (Fig. 1a), and both Tas2r138 and Tas2r114 were highly expressed in AMs (Fig. 1b) upon P. aeruginosa infection, which is in good agreement with its protein expressions determined by immunofluorescence staining (Fig. 1c, d)

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Summary

Introduction

Taste is one of the most important sensing functions in mammals, among which bitterness is one of the five basic tastes. A mild bitter taste produces an unpleasant sensation, while a strong bitter taste causes nausea, vomiting, and physical disgust. The perception of bitter taste is one of the body’s effective self-protection mechanisms to prevent the intake of harmful substances.[1] It was thought that some people are sensitive to bitterness because they have more taste buds on their tongues than others. One of the family members—mouse bitter taste receptor type-2 member 138

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