Calprotectin (S100A8/A9) Is an Innate Immune Effector in Experimental Periodontitis

Infect Immun. 2021 Sep 16;89(10):e0012221. doi: 10.1128/IAI.00122-21. Epub 2021 Jun 7.


Upregulated in inflammation, calprotectin (complexed S100A8 and S100A9; S100A8/A9) functions as an innate immune effector molecule, promoting inflammation, and also as an antimicrobial protein. We hypothesized that antimicrobial S100A8/A9 would mitigate change to the local microbial community and promote resistance to experimental periodontitis in vivo. To test this hypothesis, S100A9-/- and wild-type (WT; S100A9+/+) C57BL/6 mice were compared using a model of ligature-induced periodontitis. On day 2, WT mice showed fewer infiltrating innate immune cells than S100A9-/- mice; by day 5, the immune cell numbers were similar. At 5 days post ligature placement, oral microbial communities sampled with swabs differed significantly in beta diversity between the mouse genotypes. Ligatures recovered from molar teeth of S100A9-/- and WT mice contained significantly dissimilar microbial genera from each other and the overall oral communities from swabs. Concomitantly, the S100A9-/- mice had significantly greater alveolar bone loss than WT mice around molar teeth in ligated sites. When the oral microflora was ablated by antibiotic pretreatment, differences disappeared between WT and S100A9-/- mice in their immune cell infiltrates and alveolar bone loss. Calprotectin, therefore, suppresses emergence of a dysbiotic, proinflammatory oral microbial community, which reduces innate immune effector activity, including early recruitment of innate immune cells, mitigating subsequent alveolar bone loss and protecting against experimental periodontitis.

Keywords: calprotectin; experimental periodontitis; inflammation; innate immunity; microbiome.

Publication types

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

MeSH terms

  • Alveolar Bone Loss / immunology
  • Animals
  • Dysbiosis / immunology
  • Immunity, Innate / immunology*
  • Inflammation / immunology
  • Leukocyte L1 Antigen Complex / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Periodontitis / immunology*


  • Leukocyte L1 Antigen Complex