Gingival solitary chemosensory cells are immune sentinels for periodontitis

Nat Commun. 2019 Oct 3;10(1):4496. doi: 10.1038/s41467-019-12505-x.

Abstract

Solitary chemosensory cells (SCCs) are epithelial sentinels that utilize bitter Tas2r receptors and coupled taste transduction elements to detect pathogenic bacterial metabolites, triggering host defenses to control the infection. Here we report that SCCs are present in mouse gingival junctional epithelium, where they express several Tas2rs and the taste signaling components α-gustducin (Gnat3), TrpM5, and Plcβ2. Gnat3-/- mice have altered commensal oral microbiota and accelerated naturally occurring alveolar bone loss. In ligature-induced periodontitis, knockout of taste signaling molecules or genetic absence of gingival SCCs (gSCCs) increases the bacterial load, reduces bacterial diversity, and renders the microbiota more pathogenic, leading to greater alveolar bone loss. Topical treatment with bitter denatonium to activate gSCCs upregulates the expression of antimicrobial peptides and ameliorates ligature-induced periodontitis in wild-type but not in Gnat3-/- mice. We conclude that gSCCs may provide a promising target for treating periodontitis by harnessing innate immunity to regulate the oral microbiome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Chemoreceptor Cells / immunology*
  • Chemoreceptor Cells / metabolism
  • Disease Models, Animal
  • Female
  • Gingiva / cytology
  • Gingiva / immunology*
  • Gingiva / microbiology
  • HEK293 Cells
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Humans
  • Immunity, Innate*
  • Male
  • Mice
  • Mice, Knockout
  • Microbiota / immunology*
  • Mouth Mucosa / cytology
  • Mouth Mucosa / immunology
  • Mouth Mucosa / metabolism
  • Periodontitis / immunology*
  • Periodontitis / microbiology
  • Phospholipase C beta / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / immunology
  • TRPM Cation Channels / metabolism

Substances

  • Receptors, G-Protein-Coupled
  • TRPM Cation Channels
  • Trpm5 protein, mouse
  • Phospholipase C beta
  • Plcb2 protein, mouse
  • GNAT3 protein, mouse
  • Heterotrimeric GTP-Binding Proteins