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Commensal oral microbiota induces osteoimmunomodulatory effects separate from systemic microbiome in mice
Jessica D. Hathaway-Schrader, … , Caroline Westwater, Chad M. Novince
Jessica D. Hathaway-Schrader, … , Caroline Westwater, Chad M. Novince
Published January 25, 2022
Citation Information: JCI Insight. 2022;7(4):e140738. https://doi.org/10.1172/jci.insight.140738.
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Research Article Bone biology Microbiology

Commensal oral microbiota induces osteoimmunomodulatory effects separate from systemic microbiome in mice

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Abstract

Commensal microbes critically regulate skeletal homeostasis, yet the impact of specific microbiota communities on osteoimmune response mechanisms is unknown. To discern osteoimmunomodulatory effects imparted by the commensal oral microbiota that are distinct from the systemic microbiota, osteoimmunology studies were performed in both alveolar bone and nonoral skeletal sites of specific pathogen–free (SPF) versus germ-free (GF) mice and SPF mice subjected to saline versus chlorhexidine oral rinses. SPF versus GF mice had reduced cortical/trabecular bone and an enhanced pro-osteoclastic phenotype in alveolar bone. TLR signaling and Th17 cells that have known pro-osteoclastic actions were increased in alveolar BM, but not long BM, of SPF versus GF mice. MHC II antigen presentation genes and activated DCs and CD4+ T cells were elevated in alveolar BM, but not long BM, of SPF versus GF mice. These findings were substantiated by in vitro allostimulation studies demonstrating increased activated DCs derived from alveolar BM, but not long BM, of SPF versus GF mice. Chlorhexidine antiseptic rinse depleted the oral, but not gut, bacteriome in SPF mice. Findings from saline- versus chlorhexidine-treated SPF mice corroborated outcomes from SPF versus GF mice, which reveals that the commensal oral microbiota imparts osteoimmunomodulatory effects separate from the systemic microbiome.

Authors

Jessica D. Hathaway-Schrader, Johannes D. Aartun, Nicole A. Poulides, Megan B. Kuhn, Blakely E. McCormick, Michael E. Chew, Emily Huang, Richard P. Darveau, Caroline Westwater, Chad M. Novince

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Figure 1

Commensal microbiota has proinflammatory immunostimulatory effects in barrier periodontal tissues.

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Commensal microbiota has proinflammatory immunostimulatory effects in ba...
(A) Representative H&E-stained sections of junctional epithelium and gingival connective tissue at the buccal aspect of the mandibular first molar (×200). (B) Inflammatory cell infiltrate within junctional epithelium and gingival connective tissue of the mandibular first molar; cell area per tissue area (%); n = 4/gp. (C) qPCR analysis of Tnf mRNA in mandibular gingiva; n = 4–5/gp. (D) Sagittal sections of maxillae were stained with LYVE-1–FITC; representative immunofluorescence of LYVE-1 in the interdental space between first and second molars (×200). (E–N) Flow cytometric analysis evaluated proinflammatory innate immune cells in oral draining cervical lymph nodes (CLNs); n = 4/gp. (E) Representative gating strategy for neutrophils and monocytes. Representative dot plots and quantitation for (F and G) CD11b+Ly6C–Ly6G+ neutrophils and (H and I) CD11b+Ly6ChiLy6G–F4/80+ inflammatory monocytes; reported as percentage of CD11b+ cells. (J) Representative gating strategy for M1 and M2 macrophages. Representative dot plots and quantitation for (K and L) CD11b+MHC II+CD68+CD64+CD206– M1 macrophages and (M and N) CD11b+MHC II+CD68+CD64–CD206+ M2 macrophages; reported as percentage of CD11b+ cells. Unpaired t test; data presented as mean ± SEM; *P < 0.05, **P < 0.01.

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