SPLTRAK Abstract Submission
Ajinomoto Award for Young Investigators: Solitary Chemosensory Cells Function As A Double-Edged Sword: Protective Sentinels Against Pathogens But Also Initiators Of Inflammation And Disease.
Marco Tizzano
Monell Chemical Senses Center, , ,

For a hundred years, researchers have known there is a population of epithelial cells with a tear/blob shape and a top brush of microvilli, named tuft, brush or solitary chemosensory cells (SCCs) depending on the mucosa that harbors them. What has been discovered in the last two-three decades is that these SCC-like cells display chemosensory capabilities and they harbor the same chemical-sensing taste receptors/downstream signaling pathway as do the tongue taste buds. SCCs are stationed in the lining mucosa of many body structures and organs including the nasal passages, intestines, lungs, pancreas, gallbladder, urethra, and more. A wave of recent research has revealed that SCCs serve as sentinels along the body's invasion routes, sensing pathogens and chemicals that are either inhaled or that attempt to infiltrate in other ways. Although not part of the immune or nervous system, SCCs interact with these systems to help coordinate protective responses against the xenobiotic invasion. But SCCs can also betray us; they are implicated in airway inflammatory conditions such as asthma and rhino-sinusitis or in other diseases such as cancer, flu and allergies. Research in my lab attempts to shed some of the mysteries of SCCs: (1) what pathogen molecules and allergens SCCs recognize, (2) which receptors and downstream mechanisms they deploy to sense pathogens, (3) what is the interaction of SCCs and the innate immune system, and (4) how do SCCs contribute to certain respiratory and oral diseases, and (5) how can SCCs be harnessed to become a major target of medical treatments. Our work is now hinting that SCCs in the respiratory system drive conditions such as allergies, asthma, and sinus inflammation. Our data show that whereas acute exposure to bacterial quorum sensing molecules stimulates the immune system upon activation of the SCCs, repeated long-term activation of the SCC pathway leads to chronic airway inflammation. Moreover, in the oral cavity, SCCs interact with the gingival microbiota and have a leading role in periodontitis, perhaps by releasing the same immune-stimulating molecules that trigger defenses against pathogens. In summary, stimulating SCCs can reduce bacterial invasions but, in contrast, blocking or stimulating with benign triggers these cells can help ease asthma, allergy symptoms, and periodontitis. Our research provides foundational basic science and explores how to translate this into novel approaches to promote health and treat mucosal inflammatory conditions.