Divergent roles of Toll-like receptor 2 in response to lipoteichoic acid and Staphylococcus aureus in vivo
Divergent roles of Toll-like receptor 2 in response to lipoteichoic acid and Staphylococcus aureus in vivo
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DOI：
10.1002/eji.200939929
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发表时间：
2010-06-01
影响因子：
5.4
通讯作者：
Ho, May
中科院分区：
文献类型：
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作者：
Gillrie, Mark R.;Zbytnuik, Lori;Ho, May
白细胞对脂磷壁酸（LTA）（金黄色葡萄球菌的TLR 2依赖性主要细胞壁成分）的反应与感染的结果有关。在这项研究中，我们研究了非造血TLR 2在LTA和S。通过创造骨髓嵌合体来获得金黄色葡萄球菌。在WT C57 BL/6和TLR 2（-/-）双右箭头WT小鼠中，响应于LTA的显著白细胞募集需要IFN-γ引发，但在TLR 2（-/-）或WT双右箭头TLR 2（-/-）动物中未观察到。LTA还在IFN-γ致敏的原代人微血管内皮细胞中诱导促炎反应，导致体外白细胞募集。当小鼠感染S.在金黄色葡萄球菌中，在TLR 2（-/-）和TLR 2（-/-）双右箭头WT小鼠中观察到TNF-α和IL-6的最显著升高。与WT小鼠相比，TLR 2（-/-）而非嵌合小鼠表现出增加的IL-17、血液白细胞增多和肺嗜中性粒细胞增多。总的来说，这些结果表明IFN-γ和非造血TLR 2对LTA引起的白细胞募集起着重要作用。相反，造血细胞和非造血细胞上的TLR 2似乎协调了对S.金黄色葡萄球菌中，使得在完全TLR 2缺陷中，存在过度的促炎反应和/或免疫反应向Th 17表型的偏移，这可能导致TLR 2（-/-）小鼠的存活率降低。
The response of leukocytes to lipoteichoic acid (LTA), a TLR2-dependent major cell wall component of Staphylococcus aureus, is linked to the outcome of an infection. In this study we investigated the role of nonhematopoietic TLR2 in response to LTA and S. aureus by creating bone marrow chimeras. Significant leukocyte recruitment in response to LTA required IFN-gamma priming in WT C57BL/6 and TLR2(-/-) double right arrow WT mice, but was not observed in TLR2(-/-) or WT double right arrow TLR2(-/-) animals. LTA also induced a proinflammatory response in IFN-gamma primed primary human microvascular endothelial cells leading to leukocyte recruitment in vitro. When mice were infected with S. aureus, the most profound elevation of TNF-alpha and IL-6 was seen in TLR2(-/-) and TLR2(-/-) double right arrow WT mice. TLR2(-/-), but not chimeric mice, demonstrated increased IL-17, blood leukocytosis and pulmonary neutrophilia compared to WT mice. Collectively, the results suggest an essential role for IFN-gamma and nonhematopoietic TLR2 for leukocyte recruitment in response to LTA. In contrast, TLR2 on both hematopoietic and nonhematopoietic cells appears to orchestrate an inhibitory response to S. aureus such that in complete TLR2 deficiency, there is an exaggerated proinflammatory response and/or skewing of the immune response towards a Th17 phenotype that may contribute to the decreased survival of TLR2(-/-) mice.