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Originally published online as doi:10.1189/jlb.0708428 on December 31, 2008

Published online before print December 31, 2008
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(Journal of Leukocyte Biology. 2009;85:648-655.)
© 2009 by Society for Leukocyte Biology

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

Hyunjin Shin*,1, Yue Zhang*,1, Madhumita Jagannathan{dagger}, Hatice Hasturk{ddagger}, Alpdogan Kantarci{ddagger}, Hongsheng Liu{ddagger}, Thomas E. Van Dyke{ddagger}, Lisa M. Ganley-Leal§,3 and Barbara S. Nikolajczyk*,2,3

* Departments of Microbiology and
{dagger} Pathology, Boston University School of Medicine, and
{ddagger} Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts, USA; and
§ Department of Medicine, Section of Infectious Diseases, Evans Biomedical Research Center, Boston Medical Center, Boston, Massachusetts, USA

2 Correspondence: Boston University School of Medicine, Department of Microbiology, 72 E. Concord Street, L-516, Boston, MA 02118, USA. E-mail: bnikol{at}bu.edu

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-1β, 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-1β 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.

Key Words: human • bacterial infection • inflammation • gene regulation • molecular biology




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