Role of toll-like receptor 4 in gram-positive and gram-negative pneumonia in mice

Role of toll-like receptor 4 in gram-positive and gram-negative pneumonia in mice
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DOI:
10.1128/iai.72.2.788-794.2004
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发表时间:
2004-02-01
影响因子:
3.1
通讯作者:
van der Poll, T
van der Poll, T
中科院分区:
医学2区
文献类型:
--
作者:
Branger, J;Knapp, S;van der Poll, T

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为探讨Toll样受体4(TLR4)在肺炎免疫应答中的作用,用肺炎链球菌(一种常见的革兰氏阳性呼吸道病原体)或肺炎克雷伯菌(一种常见的革兰氏阴性呼吸道病原体)经鼻腔感染C3H/HeJ小鼠(表现为突变的TLR4)和C3H/Hen野生型小鼠。在肺炎球菌肺炎的病例中,TLR4突变小鼠只有在低水平的细菌剂量感染后才表现出存活率下降,这与感染后48小时肺内的细菌负荷较高有关。在肺炎克雷伯氏菌中,TLR4突变小鼠在感染低水平或高水平细菌后表现出存活时间缩短,同时肺部细菌生长增强。这些数据表明,TLR4在肺炎球菌和克雷伯氏菌肺炎中都有助于保护性免疫反应,并且在后者(革兰氏阴性)病原体引起的呼吸道感染中发挥更重要的作用。
To determine the role of Toll-like receptor 4 (TLR4) in the immune response to pneumonia, C3H/HeJ mice (which display a mutant nonfunctional TLR4) and C3H/HeN wild-type mice were intranasally infected with either Streptococcus pneumoniae (a common gram-positive respiratory pathogen) or Klebsiella pneumoniae (a common gram-negative respiratory pathogen). In cases of pneumococcal pneumonia, TLR4 mutant mice showed a reduced survival only after infection with low-level bacterial doses, which was associated with a higher bacterial burden in their lungs 48 h postinfection. In Klebsiella pneumonia, TLR4 mutant mice demonstrated a shortened survival after infection with either a low- or a high-level bacterial dose together with an enhanced bacterial outgrowth in their lungs. These data suggest that TLR4 contributes to a protective immune response in both pneumococcal and Klebsiella pneumonia and that its role is more important in respiratory tract infection caused by the latter (gram-negative) pathogen.