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

doi:10.1128/iai.00122-21

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

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6 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 language	English (US)
Article number	e00122-21
Journal	Infection and immunity
Volume	89
Issue number	10
DOIs	https://doi.org/10.1128/iai.00122-21
State	Published - 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

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10.1128/iai.00122-21

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Johnstone, K. F., Wei, Y., Bittner-Eddy, P. D., Vreeman, G. W., Stone, I. A., Clayton, J. B., Reilly, C. S., Walbon, T. B., Wright, E. N., Hoops, S. L., Boyle, W. S., Costalonga, M., & Herzberg, M. C. (2021). Calprotectin (S100A8/A9) is an innate immune effector in experimental Periodontitis. Infection and immunity, 89(10), Article e00122-21. https://doi.org/10.1128/iai.00122-21

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title = "Calprotectin (S100A8/A9) is an innate immune effector in experimental Periodontitis",

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.",

keywords = "Calprotectin, Experimental periodontitis, Inflammation, Innate immunity, Microbiome",

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

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 {\textcopyright} 2021 American Society for Microbiology.",

year = "2021",

month = sep,

day = "16",

doi = "10.1128/iai.00122-21",

language = "English (US)",

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T1 - Calprotectin (S100A8/A9) is an innate immune effector in experimental Periodontitis

AU - Johnstone, Karen F.

AU - Wei, Yuping

AU - Bittner-Eddy, Peter D.

AU - Vreeman, Gerrit W.

AU - Stone, Ian A.

AU - Clayton, Jonathan B.

AU - Reilly, Cavan S.

AU - Walbon, Travis B.

AU - Wright, Elisa N.

AU - Hoops, Susan L.

AU - Boyle, William S.

AU - Costalonga, Massimo

AU - Herzberg, Mark C.

N1 - 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.

PY - 2021/9/16

Y1 - 2021/9/16

N2 - 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.

AB - 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.

KW - Calprotectin

KW - Experimental periodontitis

KW - Inflammation

KW - Innate immunity

KW - Microbiome

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ER -

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

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