Bitter taste receptors (T2Rs) are sentinels that coordinate metabolic and immunological defense responses

https://doi.org/10.1016/j.cophys.2021.01.006Get rights and content

In addition to being responsible for bitter taste, type 2 taste receptors (T2Rs) regulate endocrine, behavioral, and immunological responses. T2R agonists include indicators of incoming threats to metabolic homeostasis, pathogens, and irritants. This review will provide an overview of T2R-regulated processes throughout the body that function defensively. We propose a broader definition of T2Rs as chemosensory sentinels that monitor toxic, metabolic, and infectious threats and initiate defensive responses.

Section snippets

Introduction to T2Rs

Type 2 taste receptors (T2Rs) are G-protein coupled receptors (GPCRs) that were first identified in the mouth as bitter taste receptors. In humans, the T2R gene family consists of 25 functional receptor-encoding genes, many of which are polymorphic. Since their discovery, T2Rs have been identified in tissues throughout the body [1,2]. The sensory experience of bitter taste alerts animals that the potential food or drink in the mouth contains toxins or other threats. The intensity of bitterness

Endocrine Responses

Metabolic homeostasis is necessary to maintain health and prevent disease. Although themselves not directly sensing ingested sugars, T2Rs nonetheless play an important role in the regulation of blood glucose homeostasis and possibly thyroid hormone levels, which regulate overall metabolic tone. These responses play protective and defensive roles when the body is challenged with metabolic dysregulation, which can lead to life threatening diseases.

Behavioral Responses

T2Rs play an important role in the regulation of taste-related behavioral responses such as spitting out, vomiting, coughing, and sneezing. T2Rs play an important role in the regulation of these behaviors, and all serve to defend the body from pathogens, toxins, or irritants. A well-recognized function of T2Rs in the oral cavity is to trigger the rejection of strongly bitter-tasting toxins. Consuming bitter compounds can stimulate expectoration (spitting), rejection, and vomiting (see Figure 2)

Immunological Responses

T2Rs also serve as regulatory sentinels for the immune system. T2Rs have been investigated recently for their roles in immune responses throughout the body. In contrast to the behavioral and endocrine responses, the T2R-regulated immune responses defend the body against infection-causing pathogens and maintain the balance of microbiota. T2Rs have been identified in both solitary chemosensory cells (SCCs) and macrophages in mucosal tissues that form an interface between the external and internal

Conclusion

As the functions of T2Rs are identified in diverse tissues, they are increasingly characterized as defensive or protective. In the defense of endocrine homeostasis, T2Rs help regulate the incretin responses and thyroid hormone production. T2Rs also coordinate diverse immune responses in tissues frequently exposed to pathogens. T2Rs are generalized sentinels of threats to our health and function to defend the body. These protective responses occur in metabolic, immunologic, and behavioral

Conflict of interest statement

Nothing declared.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

Acknowledgements

We would like to thank Linda Flammer for her helpful comments. P.A.S.B. was supported by N.I.H.DC014286 and HATCHNJ14120.

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