Calprotectin (S100A8/A9) is an innate immune effector in experimental Periodontitis

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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, S100A92/2 and wild-type (WT; S100A91/1) C57BL/6 mice were compared using a model of ligature-induced periodontitis. On day 2, WT mice showed fewer infiltrating innate immune cells than S100A92/2 mice; by day 5, the immune cell numbers were similar. At 5days post ligature placement, oral microbial communities sampled with swabs differed significantly in beta diversity between the mouse genotypes. Ligatures recovered from molar teeth of S100A92/2 and WT mice contained significantly dissimilar microbial genera from each other and the overall oral communities from swabs. Concomitantly, the S100A92/2 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 S100A92/2 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.

Original languageEnglish (US)
Article numbere00122-21
JournalInfection and immunity
Volume89
Issue number10
DOIs
StatePublished - Sep 16 2021

Bibliographical note

Funding Information:
This work was supported by grants NIH/NIDCR 1R21DE025711 and NIH/NIDCR 1 R01DE021206 (to M.C.H.), NIH/NIDCR 1 T90 DE022732 (to M.C.H. and W.S.B.), 5F32DE028174 (W.S.B.), DE025882 (P.D.B.-E.), DE022858 (M.C.), and DE026209 (M.C.), and the Schaffer Chair for Periodontal Research at the University of Minnesota. Additional support was provided by the Office of the Vice President for Research University of Minnesota and the Associate Dean for Research, School of Dentistry. We thank the lab of Dan Knights, Department of Computer Science and Engineering at the University of Minnesota, for helpful discussions about microbiome analyses.

Funding Information:
This work was supported by grants NIH/NIDCR 1R21DE025711 and NIH/NIDCR 1 R01DE021206 (to M.C.H.), NIH/NIDCR 1 T90 DE022732 (to M.C.H. and W.S.B.), 5F32DE028174 (W.S.B.), DE025882 (P.D.B.-E.), DE022858 (M.C.), and DE026209 (M.C.), and the Schaffer Chair for Periodontal Research at the University of Minnesota. Additional support was provided by the Office of the Vice President for Research University of Minnesota and the Associate Dean for Research, School of Dentistry.

Publisher Copyright:
Copyright © 2021 American Society for Microbiology.

Keywords

  • Calprotectin
  • Experimental periodontitis
  • Inflammation
  • Innate immunity
  • Microbiome

PubMed: MeSH publication types

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

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