TLR2 介导对活表皮葡萄球菌的识别和清除菌血症。
TLR2 mediates recognition of live Staphylococcus epidermidis and clearance of bacteremia.
机构信息
School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
出版信息
PLoS One. 2010 Apr 9;5(4):e10111. doi: 10.1371/journal.pone.0010111.
BACKGROUND
Staphylococcus epidermidis (SE) is a nosocomial pathogen that causes catheter-associated bacteremia in the immunocompromised, including those at the extremes of age, motivating study of host clearance mechanisms. SE-derived soluble components engage TLR2; but additional signaling pathways have also been implicated, and TLR2 can play complex, at times detrimental, roles in host defense against other Staphylococcal spp. The role of TLR2 in responses of primary blood leukocytes to live SE and in clearance of SE bacteremia, the most common clinical manifestation of SE infection, is unknown.
METHODOLOGY/PRINCIPAL FINDINGS: We studied TLR2-mediated recognition of live clinical SE strain 1457 employing TLR2-transfected cells, neutralizing anti-TLR antibodies and TLR2-deficient mice. TLR2 mediated SE-induced cytokine production in human embryonic kidney cells, human whole blood and murine primary macrophages, in part via recognition of a soluble TLR2 agonist. After i.v. challenge with SE, early (1 h) cytokine/chemokine production and subsequent clearance of bacteremia (24-48 h) were markedly impaired in TLR2-deficient mice.
CONCLUSIONS/SIGNIFICANCE: TLR2 mediates recognition of live SE and clearance of SE bacteremia in vivo.
背景
表皮葡萄球菌（SE）是一种医院获得性病原体，可导致免疫功能低下者发生导管相关性菌血症，包括年龄处于极值的人群，这促使人们研究宿主清除机制。SE 衍生的可溶性成分与 TLR2 结合；但其他信号通路也被牵连进来，TLR2 在宿主防御其他葡萄球菌属的其他病原体时可以发挥复杂的、有时是有害的作用。TLR2 在对活的 SE 及清除 SE 菌血症（SE 感染的最常见临床表现）的原代血白细胞反应中的作用尚不清楚。
方法/主要发现：我们使用 TLR2 转染细胞、中和抗 TLR 抗体和 TLR2 缺陷小鼠研究了 TLR2 介导的对活的临床 SE 株 1457 的识别。TLR2 介导 SE 诱导人胚肾细胞、人全血和鼠原代巨噬细胞中的细胞因子产生，部分通过识别可溶性 TLR2 激动剂。在 SE 静脉内攻击后，TLR2 缺陷小鼠的早期（1 小时）细胞因子/趋化因子产生和随后的菌血症清除（24-48 小时）明显受损。
结论/意义：TLR2 介导对活 SE 的识别和体内 SE 菌血症的清除。
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