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B cells from periodontal disease patients express surface Toll‐like receptor 4
Author(s) -
Shin Hyunjin,
Zhang Yue,
Jagannathan Madhumita,
Hasturk Hatice,
Kantarci Alpdogan,
Liu Hongsheng,
Dyke Thomas E.,
GanleyLeal Lisa M.,
Nikolajczyk Barbara S.
Publication year - 2009
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0708428
Subject(s) - tlr4 , proinflammatory cytokine , biology , inflammation , toll like receptor , immunology , myeloid , receptor , microbiology and biotechnology , innate immune system , immune system , biochemistry
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.