Toll-like receptor 2 does not contribute to host response during postinfluenza pneumococcal pneumonia

Toll-like receptor 2 does not contribute to host response during postinfluenza pneumococcal pneumonia
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DOI:
10.1165/rcmb.2006-0166oc
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发表时间:
2007-05-01
影响因子:
6.4
通讯作者:
van der Poll, Tom
van der Poll, Tom
中科院分区:
医学1区
文献类型:
--
作者:
Dessing, Mark C.;van der Sluijs, Koenraad F.;van der Poll, Tom

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甲型流感可能会并发继发性细菌性肺炎,这种肺炎最常见的是由肺炎链球菌引起,并与不受控制的肺部炎症有关。有证据表明 Toll 样受体 (TLR) 2 可能是这种过度肺部炎症的介质:(1) TLR2 是革兰氏阳性刺激最重要的“传感器”,(2) TLR2 有助于肺炎链球菌诱导的炎症,(3) 甲型流感可增强各种细胞类型中的 TLR2 表达。因此,本研究的目的是确定 TLR2 在宿主对流感后肺炎球菌肺炎反应中的作用。 TLR2 敲除 (KO) 和野生型 (WT) 小鼠经鼻内感染甲型流感病毒。十四天后,他们鼻内注射肺炎链球菌。 TLR2 KO 和 WT 小鼠中流感与类似的短暂体重减轻有关。两种小鼠品系均在第 14 天完全康复并完全清除了病毒。重要的是,在流感后肺炎球菌肺炎期间,TLR2 KO 和 WT 小鼠在细菌生长、肺部炎症或细胞因子/趋化因子浓度方面没有检测到差异,除了 TLR2 KO 小鼠中细胞因子诱导的中性粒细胞趋化因子的肺部水平较低之外。 Toll 样受体 2 在小鼠流感后肺炎球菌肺炎期间不参与宿主防御。
Influenza A can be complicated by secondary bacterial pneumonia, which is most frequently caused by Streptococcus pneumoniae and associated with uncontrolled pulmonary inflammation. Evidence points to Toll-like receptor (TLR) 2 as a possible mediator of this exaggerated lung inflammation: (1) TLR2 is the most important "sensor" for gram-positive stimuli, (2) TLR2 contributes to S. pneumoniae-induced inflammation, and (3) influenza A enhances TLR2 expression in various cell types. Therefore, the objective of this study was to determine the role of TLR2 in the host response to postinfluenza pneumococcal pneumonia. TLR2 knockout (KO) and wild-type (WT) mice were infected intranasally with influenza A virus. Fourteen days later they were administered with S. pneumoniae intranasally. Influenza was associated with a similar transient weight loss in TLR2 KO and WT mice. Both mouse strains were fully recovered and had completely cleared the virus at Day 14. Importantly, no differences between TLR2 KO and WT mice were detected during postinfluenza pneumococcal pneumonia with respect to bacterial growth, lung inflammation, or cytokine/chemokine concentrations, with the exception of lower pulmonary levels of cytokine-induced neutrophil chemoattractant in TLR2 KO mice. Toll-like receptor 2 does not contribute to host defense during murine postinfluenza pneumococcal pneumonia.