Dysfunctional innate immune responsiveness to Porphyromonas gingivalis lipopolysaccharide in diabetes

Introduction: Type 1 diabetes is a major risk factor for the development of severe periodontal disease. As diabetes increases in severity, so does the susceptibility to and severity of periodontitis. People with diabetes who have periodontal disease have a harder time maintaining healthy blood glucose levels. Macrophages play an important role in both diabetes and periodontitis. Previous research comparing bone-marrow-derived macrophages (BM-M phi) from diabetic non-obese diabetic (NOD) mice and control mice illustrates that a dysregulation in cytokine, Toll-like receptor (TLR) expression, and cell signaling occurs in the diabetic state. Methods: This study examines the effect of chronic hyperglycemia on BM-M phi TLR expression and activation, cell signaling, cytokine production, and phagocytic function in the diabetic state, when challenged with the periodontal stimulus Porphyromonas gingivalis lipopolysaccharide (LPS) to further understand how diabetes and associated hyperglycemia may contribute to the increased susceptibility of people with diabetes to periodontitis. Results: When BM-M phi, obtained from diabetic NOD mice, are stimulated with P. gingivalis LPS under hyperglycemic conditions the following changes occur: reduced messenger RNA expression and cell surface expression of TLR2, reduced messenger RNA expression and protein production of tumor necrosis factor-alpha, reduced signal transduction, and a reduction in phagocytic function. All the activity of BM-M phi from diabetic NOD mice was restored when differentiation and stimulation occurred under normoglycemic conditions. Discussion: Diabetic patients in a hyperglycemic state may be generating macrophages that are inherently immunocompromised, contributing to an environment allowing periodontal infections to flourish. As a consequence, people with diabetes who maintain proper control of blood sugar levels may experience an increased immunological benefit when challenged with a periodontal infection.