B cells from periodontal disease patients express surface Toll-like receptor 4

Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
Journal of leukocyte biology (Impact Factor: 4.29). 04/2009; 85(4):648-55. DOI: 10.1189/jlb.0708428
Source: PubMed


Chronic systemic inflammation links periodontal disease (PD) to increased incidence of cardiovascular disease. Activation of TLRs, particularly TLR4, promotes chronic inflammation in PD by stimulating myeloid cells. B cells from healthy individuals are generally refractory to TLR4 agonists as a result of low surface TLR4 expression. Unexpectedly, a significantly increased percentage of gingival and peripheral blood B cells from patients with PD expressed surface TLR4. Surface expression correlated with an active TLR4 promoter that mimicked the TLR4 promoter in neutrophils. B cells from PD patients were surface myeloid differentiation protein 2-positive and also packaged the enhancer of a proinflammatory cytokine, IL-1 beta, into an active structure, demonstrating that these cells harbor key characteristics of proinflammatory cell types. Furthermore, B cells lacked activating signatures of a natural IL-1 beta inhibitor, IL-1 receptor antagonist. Surprisingly, despite multiple signatures of proinflammatory cells, freshly isolated B cells from PD patients had decreased expression of TLR pathway genes compared with B cells from healthy individuals. Decreases in inflammatory gene expression were even more dramatic in B cells stimulated with a TLR4 ligand from a periodontal pathogen, Porphyromonas gingivalis LPS 1690. In contrast, B cell TLR4 was not activated by the prototypic TLR4 ligand Escherichia coli LPS. These findings raise the unexpected possibility that TLR4 engagement modulates B cell activation in PD patients.

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    • "Surface TLR2 expression + b Increase cytokine production À Increase cytokine production [88] [112] Surface TLR4 expression ++ Regulate cytokine production + Unknown [102] c IL-1b expression +/++ d Pro-inflammatory and pro-osteoclastogenic À/À Promotes inflammation and insulin resistance [68] [88] IL-6 expression "
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