Differential involvement of TLR2 and TLR4 in host survival during pulmonary infection with Chlamydia pneumoniae
Differential involvement of TLR2 and TLR4 in host survival during pulmonary infection with Chlamydia pneumoniae
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DOI：
10.1002/eji.200535152
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发表时间：
2006-05-01
影响因子：
5.4
通讯作者：
Miethke, Thomas
中科院分区：
文献类型：
--
作者：
Rodriguez, Nuria;Wantia, Nina;Miethke, Thomas
探讨了TLR 2和TLR 4在肺部感染时识别肺炎衣原体和在感染后存活的相关性。我们发现C. pneumoniae对TLR 2有部分依赖性，对TLR 4无依赖性。趋化因子MIP-2和MIP-1 α未被诱导，而IL-12 p40水平在TLR 2（-/-）小鼠中高于野生型小鼠。TLR 2（-/-）小鼠TNF、角质形成细胞衍生趋化因子和单核细胞趋化蛋白-1的分泌减弱，而IFN-γ的分泌与野生型小鼠一样增加。TLR 2（-/-）x TLR 4（d/d）的肺细胞因子和趋化因子应答与TLR 2（-/-）小鼠相似。TLR 2（-/-）和TLR 2（-/-）x TLR 4（d/d）小鼠也吸引更少的多形核中性粒细胞进入肺，而TLR 4（d/d）小鼠招募它们。在TLR 2（-/-）和TLR 2（-/-）x TLR 4（d/d）小鼠中，多形核中性粒细胞的减弱募集与体重减轻和感染后3天衣原体负荷降低相关。在感染后9天，TLR 2（-/-）和TLR 2（-/-）x TLR 4（d/d）小鼠与野生型小鼠一样有效地产生细胞因子和趋化因子，表明TLR在炎症中的参与随时间而变化。所有TLR 2（-/-）x TLR 4（d/d）小鼠死于感染，而约50%的TLR 2（-/-）小鼠死亡。综上所述，TLR 2和TLR 4的功能是在肺部感染C.肺炎。
The relevance of TLR2 and TLR4 for recognizing Chlamydia pneumoniae in vivo during pulmonary infection and to survive the infection was explored. We found that early immune responses triggered by C. pneumoniae partially depended on TLR2, but not on TLR4. The chemokines MIP-2 and MIP-1 alpha were not induced, while IL-12p40 levels were higher in TLR2(-/-) mice compared to wild-type mice. Secretion of TNF, keratinocyte-derived chemokine and monocyte chemoattractant protein-1 was attenuated in TLR2(-/-) mice, while IFN-gamma was increased as in wild-type mice. The pulmonary cyto- and chemokine response of TLR2(-/-) x TLR4(d/d) was similar to TLR2(-/-) mice. TLR2(-/-) and TLR2(-/-) x TLR4(d/d) mice also attracted fewer polymorphonuclear neutrophils into the lung, while TLR4(d/d) mice recruited them. Attenuated recruitment of polymorphonuclear neutrophils correlated with reduced weight loss in TLR2(-/-) and TLR2(-/-) x TLR4(d/d) mice and a lower chlamydial burden 3 days post infection. At 9 days post infection, TLR2(-/-) and TLR2(-/-) x TLR4(d/d) mice produced cyto- and chemokines as efficiently as wild-type mice, indicating that the involvement of TLR in inflammation varies over time. All TLR2(-/-) x TLR4(d/d) mice succumbed to the infection, while about 50% of TLR2(-/-) mice died. Taken together, the function of TLR2 and TLR4 is required to survive pulmonary infection with C. pneumoniae.