Research ArticleHost-Microbe Interactions

Bacterial d-amino acids suppress sinonasal innate immunity through sweet taste receptors in solitary chemosensory cells

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Sci. Signal.  05 Sep 2017:
Vol. 10, Issue 495, eaam7703
DOI: 10.1126/scisignal.aam7703

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The sweet taste of bacteria

Stimulation of the sweet taste receptor (T1R) in solitary chemosensory cells of the upper respiratory epithelium inhibits the release of antimicrobial peptides by neighboring epithelial cells. In addition to being activated by various sugars, T1R can also be activated by some d-amino acids. Lee et al. found that Staphylococcus species in the nasal cavities of chronic rhinosinusitis patients produced d-Phe and d-Leu, both of which can activate T1R. Treatment of primary human sinonasal epithelial cultures with d-Phe and d-Leu inhibited the release of antimicrobial peptides and increased cell death in response to infection with methicillin-resistant S. aureus. d-Phe and d-Leu, as well as medium conditioned by respiratory isolates of Staphylococcus, inhibited the formation of Pseudomonas aeruginosa biofilms. These findings demonstrate that d-amino acids produced by nasal flora can inhibit innate immune responses through T1R and may shape the microbial community of the airways.

Abstract

In the upper respiratory epithelium, bitter and sweet taste receptors present in solitary chemosensory cells influence antimicrobial innate immune defense responses. Whereas activation of bitter taste receptors (T2Rs) stimulates surrounding epithelial cells to release antimicrobial peptides, activation of the sweet taste receptor (T1R) in the same cells inhibits this response. This mechanism is thought to control the magnitude of antimicrobial peptide release based on the sugar content of airway surface liquid. We hypothesized that d-amino acids, which are produced by various bacteria and activate T1R in taste receptor cells in the mouth, may also activate T1R in the airway. We showed that both the T1R2 and T1R3 subunits of the sweet taste receptor (T1R2/3) were present in the same chemosensory cells of primary human sinonasal epithelial cultures. Respiratory isolates of Staphylococcus species, but not Pseudomonas aeruginosa, produced at least two d-amino acids that activate the sweet taste receptor. In addition to inhibiting P. aeruginosa biofilm formation, d-amino acids derived from Staphylococcus inhibited T2R-mediated signaling and defensin secretion in sinonasal cells by activating T1R2/3. d-Amino acid–mediated activation of T1R2/3 also enhanced epithelial cell death during challenge with Staphylococcus aureus in the presence of the bitter receptor–activating compound denatonium benzoate. These data establish a potential mechanism for interkingdom signaling in the airway mediated by bacterial d-amino acids and the mammalian sweet taste receptor in airway chemosensory cells.

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