Potential treatment strategy for sinus infections
Taste receptors have key roles in the regulation of innate immune defenses in the human respiratory tract. Bitter taste receptors (T2Rs) and sweet taste receptor (T1R2/3) are all G-protein-coupled receptors. T2Rs in the upper airway detect harmful compounds and release antimicrobial peptides to destroy these compounds. So, T2Rs are thought to be a first line of defense against sinus infections. T1R2/3, when activated, suppresses T2Rs from releasing antimicrobial peptides. Previous research has shown that sugars like glucose can activate T1R2/3.
Now a new study reveals that amino acids can also activate T1R2/3. The finding may open ways for the development of therapies for chronic sinus infections, or called chronic rhinosinusitis.
The study is co-led by Dr. Noam Cohen from the University of Pennsylvania Perelman School of Medicine and Robert Margolskee from Monell Chemical Senses Center. Dr. Cohen has been investigating upper airway mucosal innate immunity, airway taste receptors, and chronic rhinosinusitis for years.
Prior this study, Dr. Cohen and colleagues found that patients with chronic rhinosinusitis have increased glucose levels in their nasal secretions. Combined with other reports, their findings indicate that the increased glucose in respiratory secretions in diseases like chronic rhinosinusitis promotes activation of T1R2/3 and suppresses T2R-mediated innate defense. So, manipulating T2Rs and T1R2/3 represents a potential treatment strategy for chronic rhinosinusitis.
In the current study, Dr. Cohen's team tested the hypothesis that amino acids produced by bacteria in the sinonasal cavity could also activate T1R2/3. They investigated bacterial cultures grown from human sinonasal swabs from patients with chronic rhinosinusitis, and found that the bacterium Staphylococcus aureus produced at least two D-amino acids, D-Phe and D-Leu, that can activate T1R2/3. Additionally, D-amino acids derived from S. aureus inhibited the formation of Pseudomonas aeruginosa biofilms.
Dr. Cohen explained that these amino acids block the body's natural immune response by suppressing the protective T2Rs.
Together, the data suggest that D-amino acids produced by certain nasal bacteria inhibit innate immune responses by activating T1R2/3 and therefore inhibiting antimicrobial peptide secretion. This may be a strategy that S. aureus uses to avoid being cleared and to colonize human airways. Therefore, inhibiting T1R2/3 might be a treatment strategy for sinus infections.
Since D-amino acids have an impact on the bacterium P. aeruginosa, the discovery may extend our understanding of bacterial interactions in the human airway.
The study (Bacterial D-amino acids suppress sinonasal innate immunity through sweet taste receptors in solitary chemosensory cells) appears 5 Sep 2017 in Science Signaling.