B cells promote obesity-associated periodontitis and oral pathogen-associated inflammation (IRC3P.461)

Abstract

Abstract Chronic inflammation likely underlies the predisposition of type 2 diabetes (T2D) patients to periodontitis (PD), and the exacerbation of each disease when both are present. Several lines of evidence indicate that pro-inflammatory B cells promote T2D and PD individually, but the possibility that B cells are a key link between T2D to PD is untested. We compared outcomes from oral P. gingivalis challenge of lean WT or B cell-null mice to outcomes from mice that were obese and insulin resistance prior to oral challenge. Obese WT mice responded to oral P. gingivalis challenge with significant periodontal bone loss, while obese B cell-null mice were completely protected 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 the PD-associated cytokines TNF-α and MIP-2. B cells furthermore impact adipose tissue 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 promoting 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, and may indicate the use of B cell depletion to alleviate PD and T2D simultaneously.