Live Borrelia burgdorferi Spirochetes Elicit Inflammatory Mediators from Human Monocytes via the Toll-Like Receptor Signaling Pathway

被引:52
作者
Dennis, Vida A. [1 ]
Dixit, Saurabh [1 ]
O'Brien, Shannon M. [1 ]
Alvarez, Xavier [2 ]
Pahar, Bapi [2 ]
Philipp, Mario T. [1 ]
机构
[1] Tulane Univ, Hlth Sci Ctr, Tulane Primate Res Ctr, Div Bacteriol & Parasitol, Covington, LA 70433 USA
[2] Tulane Univ, Hlth Sci Ctr, Tulane Primate Res Ctr, Div Comparat Pathol, Covington, LA 70433 USA
基金
美国国家卫生研究院;
关键词
NF-KAPPA-B; GRAM-NEGATIVE BACTERIA; LYME-DISEASE AGENT; MATRIX METALLOPROTEINASES; CD14-DEPENDENT MECHANISM; CYTOKINE PRODUCTION; IMMUNE-RESPONSES; HUMAN PLATELETS; HUMAN-CELLS; ACTIVATION;
D O I
10.1128/IAI.01078-08
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We investigated the mechanisms that lead to the production of proinflammatory mediators by human monocytes when these cells are exposed in vitro to live Borrelia burgdorferi spirochetes. We first focused on myeloid differentiation primary response protein 88 (MyD88), an adapter molecule that is essential in the Toll-like receptor (TLR) pathway. Real-time PCR, flow cytometry, and confocal microscopy experiments revealed that MyD88 was maximally expressed in THP-1 cells after 24-h stimulation of these cells with live B. burgdorferi. Silencing of the MYD88 gene by using small interfering RNA resulted in 24%, 35%, and 84% down-modulation of the production of tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), and IL-6, respectively, in THP-1 cells stimulated with live B. burgdorferi. Specific silencing of the TLR1, TLR2, or TLR5 gene by RNA interference further revealed that silencing of the TLR1 and TLR2 genes alone or combined, but not the TLR5 gene, caused a downregulation of IL-6, IL-8, and TNF-alpha in live B. burgdorferi-stimulated THP-1 cells. Overall, similar results were obtained for THP-1 cells stimulated with purified lipoproteins. Our results indicate that the TLR pathway mediates, at least in part, the release of inflammatory mediators in human monocytes stimulated with live B. burgdorferi spirochetes and furthermore suggest that the TLR-dependent interaction between these cells and live spirochetes is mediated by spirochetal lipoproteins but not by flagellin.
引用
收藏
页码:1238 / 1245
页数:8
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