B cells promote obesity-associated periodontitis and oral pathogen-associated inflammation.
Individuals with T2D and PD suffer significantly from the ability of one disease to intensify the other. Disease-associated inflammation is one mechanism thought to fuel this pathogenic feed-forward loop. Several lines of evidence indicate that proinflammatory B cells promote T2D and PD; thus, B cells are top candidates for a cell type that predisposes PD in T2D. To test directly the role of B cells in T2D-associated PD, we compared outcomes from oral Porphyromonas gingivalis challenge of lean WT or B cell-null mice with outcomes from mice that were obese and insulin-resistant before challenge. Obese WT mice responded to oral P. gingivalis challenge with significant periodontal bone loss, whereas obese B cell-null mice were protected completely from PD. By contrast, lean WT and B cell-null mice suffer similar periodontal bone loss in response to oral pathogen. B cells from obese/insulin-resistant hosts also support oral osteoclastogenesis and both oral and systemic production of inflammatory cytokines, including pro-osteoclastogenic TNF-α and MIP-2, an ortholog of human IL-8. B cells furthermore impact AT inflammation in obese, P. gingivalis-infected hosts. Taken together, these data show that fundamentally different mechanisms regulate PD in lean and obese hosts, with B cells able to promote PD only if the hosts are "primed" by obesity. These results justify more intense analysis of obesity-associated changes in B cells that predispose PD in human T2D.
Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA;
Min
M
Zhu
Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA;
Anna C
AC
Belkina
Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA;
Jason
J
DeFuria
Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA;
Jordan D
JD
Carr
Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, Massachusetts, USA; and.
Thomas E
TE
Van Dyke
Department of Periodontology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts, USA.
Robert
R
Gyurko
Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA; bnikol@bu.edu.
Barbara S
BS
Nikolajczyk
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D054426:Chemokine CXCL2 / Q000235:genetics / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009765:Obesity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010518:Periodontitis / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D014409:Tumor Necrosis Factor-alpha
B lymphocyte; Porphyromonas gingivalis; cytokine; mouse model; type 2 diabetes