Meet the Newest Member of the Immune System: The Nose

The CruxBy Guest BloggerMar 7, 2013 1:21 AM


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By Carrie Arnold

Those with a sensitive sniffer are treated to the pleasure of subtle differences between an ’84 Bordeaux and an ’87 Cabernet, or the ability to tell whether the diner down the street is having a special on onion rings or fries. Even the non-foodies among us can tell whether a carton of milk has expired with a single sniff. But new research hints that the function of taste and smell receptors go far beyond our gourmand aspirations. Scientists have found that the proteins we use to detect certain tastes and scents are actually an important part of our immune system. Of all the classes of taste (sweet, sour, salty, bitter and umami), humans are the best at detecting bitter, and for good reason. Many of the toxins found in food are bitter, and being able to sense these in minute qualities was a great evolutionary boon to staying alive and healthy. Not surprisingly, bitter taste receptors are found in large quantities on the tongue. But a 2009 study in Science also found these receptors deep in the lungs. Otorhinolaryngologist and sinus surgeon Noam Cohen at the University of Pennsylvania went spelunking through the nose—his area of expertise—to see whether it might contain the same receptors, and found that it did. Clearly, these receptors weren’t used for taste, since food generally doesn’t enter the nasal cavity (accidentally snorted beverages aside). The Science paper indicated that the taste receptors in the lungs are used to help the body detect the presence of pathogens. Perhaps, Cohen reasoned, the receptors he found in the nose were used for the same purpose.

A taste for immunity

Cohen and colleagues at the Monell Chemical Senses Institute, also in Philadelphia, tested this hypothesis by investigating the activity of a particular bitter taste receptor known as T2R38. The scientists chose this particular receptor because it has several different variants common in humans. People with the so-called taster version of this gene are extremely sensitive to bitter tastes and can sense a bitter chemical known as phenylthiocarbamide (PTC) at very low concentrations. These people are commonly known as “supertasters,” and frequently report a dislike for bitter-tasting vegetables like broccoli. Those with the non-taster version of T2R38 can still taste bitter compounds like PTC, but it takes a much higher dose for them to respond. Cohen’s own, unpublished observations gave him the first hint that the taster version of T2R38 might be linked to resistance to infections. “We noticed that people who were supertasters—people who had both copies of the taster version of this gene—never got sinus infections from Gram negative bacteria,” Cohen said. The researchers believed that this may be because people with the taster T2R38 receptor would be better at sensing the chemical signals produced by pathogens and subsequently clearing them from the body. Since mice and other common laboratory animals don’t have an equivalent to T2R38, the researchers grew cells derived from the noses of 12 people. To these cultures, the scientists added small amounts of a chemical signaling molecule produced by Pseudomonas aeruginosa, a particularly nasty respiratory pathogen. The results, which the scientists published in the Journal of Clinical Investigation, found that cells which had taster T2R38 receptors on them responded strongly even to the tiniest quantities of the P. aeruginosa signaling molecule. Non-taster T2R38 receptors only responded when much larger quantities of the signaling molecule were present. The nasal cells responded in two interesting ways: small hairs known as cilia attached to the cells beat more strongly in the presence of the signaling molecule, and the cells secreted nitric oxide, a chemical that’s toxic to bacteria. “These cells are basically killing the bugs and sweeping them away,” Cohen explained. “So if you can taste PTC on your tongue, it means you detect these bacterial signaling molecules at very low concentrations. And when you detect these molecules, you turn on this response that kills the Pseudomonas and lo and behold, you don’t get sick.” What’s more, T2R38 is far more sensitive to bacterial signals than it is to PTC, by a factor of a thousand or more. This indicates that taste molecules may not have evolved for taste at all. Instead, they may have initially evolved to detect and clear pathogens---and over time, natural selection co-opted them to help detect food gone bad.

Animals too

Before we humans pat ourselves on the back for superior olfactory and taste skills, we must remember that we are far from the only organism whose sniffers are finely tuned to pathogens. Dogs have been trained to detect cancer by sniffing human breath or urine samples, and recently Cliff, a two-year-old beagle, has been trained to sniff out the presence of the common hospital pathogen Clostridium difficile, a harmful pathogen frequently found in hospitals. Researchers have found that even the humble fruit fly (Drosophila melanogaster) uses its nose to avoid infection. Fruit flies typically feed on yeast that grows on decomposing, fermenting foods like bananas. The yeast itself is harmless to the fly, but other harmful bacteria and fungi can also be found on the decomposing food. Fruit flies need to be able to detect any pathogens in their yeast buffet. One cue, reckoned Marcus Stensmyr at the Max Planck Institute for Chemical Ecology in Germany, might be a chemical known as geosmin, which is produced by a variety of fungi and bacteria. “It smells like wet soil,” Stensmyr said. To our noses, perhaps. But the flies have a completely different response. Through a series of experiments published in a Cell study, Stensmyr and colleages show that fruit flies consider geosmin completely repulsive. The flies are normally attracted to vinegar smells, but when the researchers paired vinegar with even a tiny amount of geosmin, the flies stayed away. Looking more closely, the researchers identified an olfactory receptor known as Or56a that was only activated by geosmin and nothing else. What’s more, sensory neurons traveled directly from Or56a in the fruit fly nose to the brain, producing a hardwired aversion to geosmin. The behavioral significance of this was indicated by a simple test. Fruit flies like to lay their eggs on yeast as well as consuming it. When given the choice to lay eggs on a standard yeast medium or yeast that also contained small amounts of the geosmin-producing bacterium Streptomyces coelicolor, the flies all preferred the plain yeast media. But Stensmyr and colleagues then had the flies choose between plain yeast and S. coelicolor that couldn’t produce geosmin. In this test, the flies laid eggs equally between both media, indicating that the scent of geosmin was the primary way the flies avoided exposing their babies to harmful microbes. Thus, though the nose’s potential in keeping us healthy is only beginning to be appreciated, it seems to be a skill that’s been conserved among various branches of the animal kingdom. A badge of pride, then, next time you turn your nose up at the Brussels sprouts---your sensitive palate may just be your secret to good health.

Carrie Arnold is a freelance science writer in Virginia. She blogs about the science of eating disorders at, and frequently covers microbiology topics for national magazines.

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