IADR Abstract Archives
Role of Lymphocytes in Obesity-Associated Periodontitis
Objectives: Destructive immune responses underlie type 2 diabetes (T2D)-associated periodontitis (PD).B cells are top candidates for driving synergistic pathology between these two diseases. Work herein directly tests the hypothesis that B cells from a T2D milieu directly promote PD.
Methods: Lean (6 wk-old) or obese (high fat diet for 10 wks; n=8/group) WT C57BL/6J and B-cell-null mice were orally infected with P. gingivalis strain A7436 or vehicle three times at two-day intervals. Alternatively, B cells from obese WT mice were transplanted into lean lymphocyte-null (RAG-/-) mice immediately prior to oral infection. Body weights and glucose tolerance test assessed obesity and metabolic health over time. Alveolar bone loss was determined by morphometric analysis six weeks post-infection. TRAP staining and immunohistochemistry (anti-B220) were performed on jaws. Gingival tissue gene expression was assessed by qRT-PCR.
Results: Bone loss following P.gingivalis challenge was similar in lean WT and B-cell-null mice compared with vehicle-treated genotype controls.In sharp contrast, results from obese mice showed oral infection with P.gingivalis induced significant bone loss in WT mice(One-way ANOVA, p<0.05), but not in obese B-cell-null mice when compared to vehicle controls. B cells from obese mouse also support oral osteoclastogenesis and gingival inflammation in vivo as evidenced by more TRAP-positive osteoclasts (t-test, P<0.05) and gingival expression of TNF-alpha (One-way ANOVA, p<0.05) in WT compared to B cell-null samples. These changes occurred despite similar weight gain and glucose intolerance in all mice. However, B cells from obese mice alone did not induce P.gingivalis-induced periodontal bone loss in lymphocyte-null mice.
Conclusions: B cells promote pathogen-induced PD in hosts that are “primed” by obesity, but not in lean hosts. However, B cells from obese mice are not able to induce pathogen-induced PD in the absence of host T cells.
Methods: Lean (6 wk-old) or obese (high fat diet for 10 wks; n=8/group) WT C57BL/6J and B-cell-null mice were orally infected with P. gingivalis strain A7436 or vehicle three times at two-day intervals. Alternatively, B cells from obese WT mice were transplanted into lean lymphocyte-null (RAG-/-) mice immediately prior to oral infection. Body weights and glucose tolerance test assessed obesity and metabolic health over time. Alveolar bone loss was determined by morphometric analysis six weeks post-infection. TRAP staining and immunohistochemistry (anti-B220) were performed on jaws. Gingival tissue gene expression was assessed by qRT-PCR.
Results: Bone loss following P.gingivalis challenge was similar in lean WT and B-cell-null mice compared with vehicle-treated genotype controls.In sharp contrast, results from obese mice showed oral infection with P.gingivalis induced significant bone loss in WT mice(One-way ANOVA, p<0.05), but not in obese B-cell-null mice when compared to vehicle controls. B cells from obese mouse also support oral osteoclastogenesis and gingival inflammation in vivo as evidenced by more TRAP-positive osteoclasts (t-test, P<0.05) and gingival expression of TNF-alpha (One-way ANOVA, p<0.05) in WT compared to B cell-null samples. These changes occurred despite similar weight gain and glucose intolerance in all mice. However, B cells from obese mice alone did not induce P.gingivalis-induced periodontal bone loss in lymphocyte-null mice.
Conclusions: B cells promote pathogen-induced PD in hosts that are “primed” by obesity, but not in lean hosts. However, B cells from obese mice are not able to induce pathogen-induced PD in the absence of host T cells.