Role of Toll-like receptor 2 in recognition of Legionella pneumophila in a murine pneumonia model
Role of Toll-like receptor 2 in recognition of Legionella pneumophila in a murine pneumonia model
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DOI：
10.1099/jmm.0.46913-0
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发表时间：
2007-03-01
影响因子：
3
通讯作者：
Yamaguchi, Keizo
中科院分区：
文献类型：
--
作者：
Fuse, Etsu T.;Tateda, Kazuhiro;Yamaguchi, Keizo
嗜肺军团菌是一种细胞内微生物，是军团病的主要病原体。虽然最近的进展已经确定Toll样受体（TLRs）作为受体识别病原体相关的分子模式在各种微生物，了解TLRs的贡献，宿主反应在L。嗜肺菌感染仍然有限。本研究探讨了TLR 2和TLR 4在小鼠L.嗜肺菌肺炎和使用骨髓来源的巨噬细胞的体外感染模型。TLR 2缺陷小鼠，而不是TLR 4缺陷小鼠，表现出更高的致死敏感性肺攻击与L。与野生型小鼠相比，嗜肺菌小鼠的肺组织中IL-6的表达显著增加（P < 0.05）。虽然在所检查的小鼠品系中未观察到肺细菌负荷的差异，但与野生型对照和TLR 4缺陷小鼠相比，在TLR 2缺陷小鼠的肺匀浆中注意到巨噬细胞炎性蛋白-2（MIP-2）、角质形成细胞衍生的细胞因子和白细胞介素（IL）-6的较低值和较高的IL-12水平。在TLR 2缺陷小鼠的肺中，炎症细胞，特别是中性粒细胞的募集受到严重干扰。在TLR 2缺陷小鼠的骨髓来源的巨噬细胞中，MIP-2的产生减少，这是对活的L. pneumophila和纯化的LPS，而不是大肠杆菌LPS。这些数据突出了TLR 2在L.小鼠嗜肺性肺炎。结果表明，TLR 2介导的识别军团菌LIPS和随后的趋化因子依赖性细胞募集可能是军团菌的关键宿主先天性反应。嗜肺性肺炎
Legionella pneumophila is an intracellular organism and the major aetiological agent of Legionnaires' disease. Although recent progress has identified Toll-like receptors (TLRs) as receptors for recognition of pathogen-associated molecular patterns in a variety of microorganisms, understanding the contribution of TLRs to the host response in L. pneumophila infection is still limited. This study examined the roles of TLR2 and TLR4 in murine L. pneumophila pneumonia and an in vitro infection model using bone-marrow-derived macrophages. TLR2-deficient mice, but not TLR4-deficient mice, demonstrated higher lethal sensitivity to pulmonary challenge with L. pneumophila than wild-type mice (P < 0.05). Although no differences in pulmonary bacterial burden were observed among the mouse strains examined, lower values of macrophage inflammatory protein-2 (MIP-2), keratinocyte-derived cytokine and interleukin (IL)-6 and higher IL-12 levels were noted in lung homogenates of TLR2-deficient mice compared with the wild-type control and TLR4-deficient mice. Recruitment of inflammatory cells, particularly neutrophils, was severely disturbed in the lungs of TLR2-deficient mice. Reduced MIP-2 production was demonstrated in bone-marrow-derived macrophages from TLR2-deficient mice in response to live L. pneumophila and purified LPS of this strain, but not Escherichia coli LPS. These data highlight the involvement and importance of TLR2 in the pathogenesis of L. pneumophila pneumonia in mice. The results showed that TLR2-mediated recognition of Legionella LIPS and subsequent chemokine-dependent cellular recruitment may be a crucial host innate response in L. pneumophila pneumonia.