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.
Highlights
The host is colonized by diverse microorganisms at mucosal barrier surfaces exposed to the external environment
The periodontal epithelium and gingival connective tissue act as a physical barrier separating the oral microbiota from the alveolar bone crest
The periodontal lymphatic vasculature extends from the junctional epithelium, through the gingival connective tissue, and penetrates the alveolar bone marrow[35,36,37,38]
Summary
The host is colonized by diverse microorganisms at mucosal barrier surfaces exposed to the external environment. Life host-microbe interactions direct the development of immunity and the establishment of a stable complex microbiota, which is referred to as the commensal (normal) microbiota[2, 3]. Throughout the host’s life, immunity is stimulated by commensal microbiota-derived ligands that signal at pattern-recognition receptor (PRR) expressing host cells. The host immune response maintains a homeostatic relationship with the commensal microbiota, but importantly, has potent indirect effects on host physiology[4, 5]. The commensal microbiota has recently been introduced as a critical regulator of physiologic osteoimmune processes in the healthy, adult skeleton, both at oral and non-oral skeletal sites[8, 12,13,14]. The impact of specific commensal microbiota communities on osteoimmune response mechanisms is unknown
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