New mission for the nose: Sniff out multiplying microbes
AURORA, Colo. – The nose is widely celebrated for its ability to detect smells and other subtle chemical cues as well as for triggering a teary-eyed response to an airborne irritant. Now University of Colorado School of Medicine scientists have found a possible new role for the nose: a first-line defender against disease-causing bacteria.
Thomas Finger, PhD, of the University of Colorado’s Rocky Mountain Taste and Smell Center, and colleagues had discovered in earlier mouse studies the presence of individual cells scattered in a part of the mouse’s nasal cavity normally reserved for respiratory, versus smell-related, activities. Each cell expresses bitter taste receptors and each is in direct contact with the trigeminal nerve—a nerve in the head that senses touch, temperature, and pain. The trigeminal nerve is responsible for your eyes watering when you cut into an onion or for the reflexive sneeze or gasp you might have when you open up a fizzy can of soda. Finger and colleagues wanted to uncover why cells in the nose would need to detect something that tastes bitter.
In new research published in the Proceedings of the National Academy of Sciences, the researchers turned their attention to key chemical signals that bacteria use to communicate with one another. Like a secret whistle in the dark of night, disease-causing bacteria produce special molecules—called quorum sensing molecules—to let each other know when their numbers are high enough to wage a more formidable invasion. In the case of some bacteria, that involves joining forces to form a biofilm, a sturdy bacterial structure that attacks respiratory tissue and is resistant to immune defenses. The researchers wondered if one type of molecule—called acyl-homserine lactones (AHLs)—given off by a large group of bacteria might be detectable by bitter taste receptors on the solitary chemosensory cells in the nasal cavity and if so, what effect this might have on the trigeminal nerve.
In this latest study, Finger and his team first tested whether solitary chemosensory cells in mice respond to AHLs, both bacterially-produced and synthetic. Using calcium as a measure of cellular responsiveness—an increase in calcium inside the cell is one of the signs that a substance is interacting with its receptor—they found that solitary chemosensory cells do respond to AHLs in concentrations typically found when bacterial populations begin to form biofilms. Next, the researchers tested whether AHLs are able to evoke a response from the trigeminal nerve in mice. Normally, when the trigeminal nerve is activated, respiration decreases. Indeed, they found that when AHLs were flowed through the mouse’s nasal cavity, the breathing rate slowed. Finally, the researchers wanted to make sure that the decrease in respiration was from the solitary chemosensory cells versus other chemically sensitive sites on the trigeminal nerve. Using knock-out mice whose T2R bitter receptors don’t function, they found that the knock-out mice did not experience a slowed breathing rate, indicating that the solitary chemosensory cells—and the bitter taste receptors that they express— are responsible for the reaction.
Finger suggests that when a small branch of a trigeminal nerve fiber in the nose is activated, it kicks off a domino effect in which substances are released and an inflammatory response is put into high gear. He says that solitary chemosensory cells in the nasal cavity will tolerate low populations of certain disease-causing bacteria, but when they sense that the bacteria are producing more quorum sensing molecules, the cells trigger an immune response before the bacteria are able to form a biofilm.
Because bacteria that live in a mouse’s nose aren’t the same as those that live in a human’s nose, the researchers are now trying to figure out if there are other quorum sensing molecules that are more likely to occur in humans. They also plan to investigate whether the knock-out mice whose T2R receptors don’t function are more susceptible to bacterial infection.
Faculty at University of Colorado’s School of Medicine work to advance science and include physicians, educators and scientists at University of Colorado Hospital, The Children’s Hospital, Denver Health, National Jewish Health, and the Denver Veterans Affairs Medical Center. Degrees offered by the School of Medicine include doctor of medicine, doctor of physical therapy, and masters of physician assistant studies. The School is located on the University of Colorado’s Anschutz Medical Campus, one of four campuses in the University of Colorado system. For additional news and information, please visit the CU Denver newsroom online.
Tonya Ewers-Maikish, CU Denver, 303.315.6374, [email protected]
Jennifer Wenger, NIDCD/NIH, 301.496.7243