Sunday, March 2, 2014

Bitter and Sweet Taste Receptors and Immunity

I've written a few times in the past about taste.  However, the molecular mechanisms that your body uses to detect taste are for more than just eating and drinking.  The proteins that your body uses to recognize certain tastes (called taste receptors) are actually important players in innate immunity in your nose.

Chronic nasal and sinus infections (called chronic sinusitis) is a major public health problem.  This disease can be caused by fungal, bacterial, or viral infections.  One out of every five antibiotic prescriptions given to adults in the US is for sinusitis, and thus this disease is a major driver for the generation of antibiotic resistant bacteria, which are becoming a major public health threat.  Not only do sinus infections dramatically reduce quality of life and make people miserable, but they also can "seed" lower airway infections.  For example, chronic bacterial inceptions in the nose can create a reservoir of bacteria which can then infect the lung.  In patients with immunocompromised airways or airways that have impaired defensive capabilities, like cystic fibrosis patients, upper respiratory infections can lead to the onset of lower respiratory infections that can eventually be fatal.

Your nose is important because it traps most of the bacteria, viruses, fungi, and particulates that you inhale on a breath-by-breath basis.  It protects your lower airway.  Most of the time, cells in your nose gets rid of all of those pathogens without you even noticing it.  However, when the nasal defenses fail, infections results.  A major question in the field of airway biology has been why some people get upper respiratory infections but others don't.  People have long suspected that there is a genetic component.  Recent studies on taste receptors suggest that taste receptors in your nose may contribute to the long-suspected genetic basis of upper airway diseases.  Read more after the jump....

We are evolutionarily driven to like the taste of sugary foods
There are five basic types of taste.  Sweet, salty, sour, savory (also called umami, which is the taste of savory amino acids like glutamate), and bitter.  What you perceive when you eat food is a complex sensation called flavor that comprises taste, smell, and mouth feel (think of mouth feel as texture).  Smell and mouth feel combine with taste to create almost infinite flavor combinations, despite the fact that there are only five types of taste.  Bitter taste is thought to be protect us from eating harmful poisons, like toxic chemicals found in plants, which is why we perceive bitter to be a "bad" taste.  Sweet taste signals the presence of beneficial nutrients (sugars) to the brain, which is why we perceive sweet to be a "good" taste."

While most people find the taste of sugar to be pleasant, there are many complex genetic variations (called polymorphisms) in taste receptors that create differences in individual ability to taste certain bitter compounds.   There are at least 25 different bitter taste receptors, and these genetic variations (polymorphisms) in these receptors underlie the complexity of individual taste preferences for bitter foods, such as scotch, beer, coffee, and leafy green vegetables.  Some people like bitter foods and others don't.  Most often, people who don't like bitter foods have an increased bitter taste receptor function that causes the bitter compounds in these foods to taste more bitter and more unpleasant.  While these people may not be able to enjoy the taste of brussels sprouts, they may actually have better immunity in their upper airways.

Several studies have previously shown that taste receptors are expressed in other tissues beyond the tongue.  One of these locations is in the airway.   A recent paper published in the Journal of Clinical Investigation shows that bitter taste receptors and sweet taste receptors in the nose are responsible for detecting bacteria in the nose and activating defense responses, including the secretion of small proteins (peptides) that can kill bacteria.    

In a previous paper, these researchers showed that one particular bitter taste receptor, T2R38, is expressed in the nose and detects chemicals produced by a certain type of pathogenic bacteria (Pseudomonas aeruginosa).  People who have functional T2R38 (T2R38 "tasters") can detect bacteria better than people who have nonfunctional T2R38 ("non tasters"), and these T2R38 "tasters" appear to be protected against upper respiratory infection by Pseudomonas.  Genetic variation in the T2R38 bitter taste receptor has now been linked to risk for chronic sinusitis by two separate studies in US and Canadian populations.

These studies have shown that "taste" receptors are for more than just taste, as they demonstrate that bitter taste receptors are actually important components of nasal immunity.  Targeting these receptors by using compounds that can activate them may be a useful therapeutic by activating nasal defense responses and perhaps avoid the need to prescribe antibiotics in some cases.  This may help the

The more recent paper published this month now shows that sweet taste receptors also play an important role in upper respiratory defense against bacteria.  Bacteria feed on sugar present in airway mucus.  This sugar normally activates the sweet taste receptor on airway cells and represses the bitter-receptor-activated response.  It is thought that, during infection, bacteria consume the sugar and the sweet receptor is no longer activated, allowing the bitter receptors to stimulate an innate immune response.  Thus, it appears that innate immunity is partially regulated by the balance of bitter and sweet signals that are detected by the taste receptors in the nasal cells.  This may play an important role in telling the cells when bacteria are actually a "threat," as they only start to deplete the airway glucose when the bacteria reach a high number that precedes a potential infection.

This result may have important implications for diabetic patients, how have previously been shown to have elevated sugar in their nasal mucus.  Diabetic patients have long been known to have a higher rate of airway and other infections, and excess sugar in their nasal mucus may help to "mask" the presence of bacteria and delay the appropriate immune responses.  Chemicals such as lactisole or gymnemic acid, which block the sweet taste receptor, might be useful therapies for such patients by preventing the excess nasal sugar from activating sweet taste receptors in the nose even in the presence of invading bacteria.

The immune system has been suggested to be the sixth human sense.  Just like our senses of sight, hearing, taste, smell, and touch tell us about the world around us, the immune system alerts us (albeit often subconsciously) to the presence of invading pathogens.  Thinking about immunity in this light, it makes sense that the same receptors we use to detect chemical signals in one sense (taste) are also used to detect chemical signals from bacteria that are important in immunity.  We need to start thinking about these "taste" receptors as begin good for much more than just taste.  

Sources and Further Reading
  • N. Chaudhari and S.D. Roper.  "The Cell Biology of Tate."  Journal of Cell Biology.  2010.  190:285-296.  Available here.
  • S.C. Kinnamon.  "Taste Receptor Signaling - From Tongues to Lungs."  Acta Physiolica.  2012.  204:158-68.  Available here.
  • R.J. Lee, et al.  "T2R38 Taste Receptor Polymorphisms Underly Susceptibility to Upper Respiratory Tract Infection."  Journal of Clinical Investigation.  2012.  122:4145-4159.  Available here
  • R.J. Lee, et al.  "Bitter and Sweet Taste Receptors Regulate Human Upper Respiratory Innate Immunity."  Journal of Clinical Investigation.  2014.  Available here.
  • J. McDonald.  "Sweet Taste Receptors in the Nose Tell Immune System When to Kick in, Penn Team Finds."  WHYY NPR Newsworks.  2-26-14   Available here.  
  • Sweet Receptors Act as Sentinels in Defense Against Upper Airway Bacterial Infections.  Science Codex.  2-18-14.  Available here.
  • N. Shute.  "A Nose Tuned In To Bitter May Help Stave Off Sinus Infection."  NPR The Salt Blog.  10-15-12.  Available here.
  • T. Stokes.  "People Better at Tasting Bitter May Have Stronger Immunity."  FoxNews Health.  10-9-12.  Available here.
  • V.K. Viswanathan.  "Sensing bacteria, without bitterness?"  Gut Microbes.  2013.  4:91-93.  Available here.


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