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

Johnstone, Karen F; Wei, Yuping; Bittner-Eddy, Peter D; Vreeman, Gerrit W; Stone, Ian A; Clayton, Jonathan B; Reilly, Cavan S; Walbon, Travis B; Wright, Elisa N; Hoops, Susan L; Boyle, William S; Costalonga, Massimo; Herzberg, Mark C

Upregulated in inflammation, calprotectin (complexed S100A8 and S100A9; S100A8/A9) functions as an innate immune effector molecule, promoting inflammation, and 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 pre-treatment, 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.