Decreased inflammatory response in Toll-like receptor 2 knockout mice is associated with exacerbated Pneumocystis pneumonia
Decreased inflammatory response in Toll-like receptor 2 knockout mice is associated with exacerbated Pneumocystis pneumonia
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DOI：
10.1016/j.micinf.2007.12.014
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发表时间：
2008-04-01
影响因子：
5.8
通讯作者：
Lee, Chao-Hung
中科院分区：
文献类型：
--
作者：
Wang, Shao-Hung;Zhang, Chen;Lee, Chao-Hung
肺孢子虫肺炎（PcP）的特点是对肺的实质性炎症损伤。我们已经发现Toll样受体2（TLR 2）介导巨噬细胞对肺孢子虫的炎症反应，并假设TLR 2缺乏会导致PcP期间不太严重的炎症和较轻的肺损伤。组织学检查显示，TLR 2-/-小鼠与PeP确实表现出较轻的肺部炎症。在PcR期间，TLR 2-/-小鼠肺含有较少的TNF-α并且显示较低水平的NF-κ B活化。然而，患有PcP的TLR 2-/-小鼠显示症状和生物体负荷的严重程度增加。增加的生物体负荷可能是由于TLR 2-/-小鼠中保护机制的缺陷。诱导型一氧化氮合酶和NADPH氧化酶p47 phox的mRNA水平以及肺中的一氧化氮水平在TLR 2-/- PcP小鼠中降低。综上所述，本研究表明TLR 2介导的炎症反应在一定程度上有助于小鼠肺孢子虫生物体的清除。(C)2007年，Elsevier Masson SAS。All rights reserved.
Pneumocystis pneumonia (PcP) is marked by substantial inflammatory damage to the lung. We have found that Toll-like receptor 2 (TLR2) mediates macrophage inflammatory responses to Pneumocystis and hypothesized that TLR2 deficiency would lead to less severe inflammation and milder lung injury during PcP. Histopathology examination showed that TLR2-/- mice with PeP indeed exhibited milder pulmonary inflammation. TLR2-/- mouse lungs contained less TNF-alpha and displayed lower levels of NF-kappa B activation during PcR However, TLR2-/- mice with PcP displayed increased severity in symptoms and organism burden. The increased organism burden is likely due to defects in protective mechanisms in TLR2-/- mice. mRNA levels of the inducible nitric oxide synthase and NADPH oxidase p47phox, as well as nitric oxide levels in the lungs, were decreased in TLR2-/- PcP mice. Taken together, this study shows that TLR2-mediated inflammatory responses contribute to a certain degree to the clearance of Pneumocystis organism in mice. (C) 2007 Elsevier Masson SAS. All rights reserved.