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.

Download full-text


Available from: Barbara S Nikolajczyk
  • Source
    • "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 "
    [Show abstract] [Hide abstract]
    ABSTRACT: B lymphocytes play roles in many auto-immune diseases characterized by unresolved inflammation, and B cell ablation is proving to be a relatively safe, effective treatment for such diseases. B cells function, in part, as important sources of regulatory cytokines in auto-immune disease, but B cell cytokines also play roles in other non-auto-immune inflammatory diseases. B cell ablation may therefore benefit inflammatory disease patients in addition to its demonstrated efficacy in auto-immune disease. Current ablation drugs clear both pro- and anti-inflammatory B cell subsets, which may unexpectedly exacerbate some pathologies. This possibility argues that a more thorough understanding of B cell function in human inflammatory disease is required to safely harness the clinical promise of B cell ablation. Type 2 diabetes (T2D) and periodontal disease (PD) are two inflammatory diseases characterized by little autoimmunity. These diseases are linked by coincident presentation and alterations in toll-like receptor (TLR)-dependent B cell cytokine production, which may identify B cell ablation as a new therapy for co-affected individuals. Further analysis of the role B cells and B cell cytokines play in T2D, PD and other inflammatory diseases is required to justify testing B cell depletion therapies on a broader range of patients.
    Full-text · Article · Apr 2010 · Cytokine
  • [Show abstract] [Hide abstract]
    ABSTRACT: We have previously described a range-based neighbourhood operator and an experimentally discovered unconventional edge detector based on it. The latter relies on data fitting in a pixel neighbourhood, and has a wide dynamic range. A preliminary theoretical investigation of its basis, and some of its properties, are presented in this paper. It is revealed that the edge sensitive feature is the range of pixel values in successive pixel annuli around a central pixel. It is also shown that the edge strength at any centre pixel may be approximated, in the first instance, by the sum of the logarithms of these annular range values. The derived approximation is illustrated with a synthetic image and a mammogram.
    No preview · Conference Paper · Feb 2002
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IBD is characterized by a chronic, dysregulated immune response to intestinal bacteria. Past work has focused on the role of T cells and myeloid cells in mediating chronic gastrointestinal and systemic inflammation. Here, we show that circulating and tissue B cells from CD patients demonstrate elevated basal levels of activation. CD patient B cells express surface TLR2, spontaneously secrete high levels of IL-8, and contain increased ex vivo levels of phosphorylated signaling proteins. CD clinical activity correlates directly with B cell expression of IL-8 and TLR2, suggesting a positive relationship between these B cell inflammatory mediators and disease pathogenesis. In contrast, B cells from UC patients express TLR2 but generally do not demonstrate spontaneous IL-8 secretion; however, significant IL-8 production is inducible via TLR2 stimulation. Furthermore, UC clinical activity correlates inversely with levels of circulating TLR2+ B cells, which is opposite to the association observed in CD. In conclusion, TLR2+ B cells are associated with clinical measures of disease activity and differentially associated with CD- and UC-specific patterns of inflammatory mediators, suggesting a formerly unappreciated role of B cells in the pathogenesis of IBD.
    Full-text · Article · Aug 2009 · Journal of leukocyte biology
Show more