B cells from periodontal disease patients express surface Toll-like receptor 4.
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.
Shin
Hyunjin
H
Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
Zhang
Yue
Y
Jagannathan
Madhumita
M
Hasturk
Hatice
H
Kantarci
Alpdogan
A
Liu
Hongsheng
H
Van Dyke
Thomas E
TE
Ganley-Leal
Lisa M
LM
Nikolajczyk
Barbara S
BS
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D004926:Escherichia coli; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D010510:Periodontal Diseases / Q000276:immunology* / Q000473:pathology; D011401:Promoter Regions, Genetic; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000235:genetics / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4