Cutting edge:: Myeloid differentiation factor 88 is essential for pulmonary host defense against Pseudomonas aeruginosa but not Staphylococcus aureus
Cutting edge:: Myeloid differentiation factor 88 is essential for pulmonary host defense against Pseudomonas aeruginosa but not Staphylococcus aureus
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DOI：
10.4049/jimmunol.172.6.3377
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发表时间：
2004-03-15
影响因子：
4.4
通讯作者：
Wilson, CB
中科院分区：
文献类型：
--
作者：
Skerrett, SJ;Liggitt, HD;Wilson, CB
髓样分化因子88（MyD 88）是通过Toll样受体（TLR）和IL-1家族的受体进行信号转导所需的衔接分子。因此，MyD 88缺陷型小鼠对细菌感染高度敏感，包括金黄色葡萄球菌的全身感染。为了确定MyD 88在细菌性肺炎先天免疫中的作用，我们将MyD 88缺陷型和野生型小鼠暴露于雾化的铜绿假单胞菌或S.金黄色。正如预测的那样，MyD 88缺陷型小鼠在感染铜绿假单胞菌后未能产生早期细胞因子或炎症反应或控制细菌复制，导致坏死性肺炎和死亡。相比之下，MyD 88缺陷小鼠控制S.金黄色葡萄球菌感染，尽管钝化局部细胞因子和炎症反应。因此，尽管MyD 88依赖性信号传导对于下呼吸道感染后对两种病原体的细胞因子和炎症反应的起始是不可或缺的，但MyD 88对于对铜绿假单胞菌的先天免疫是必需的，而不是S.金黄色。
Myeloid differentiation factor 88 (MyD88) is an adapter molecule required for signal transduction via Toll-like receptors (TLRs) and receptors of the IL-1 family. Consequently, MyD88-deficient mice are highly susceptible to bacterial infections, including systemic infection with Staphylococcus aureus. To determine the role of MyD88 in innate immunity to bacterial pneumonia, we exposed MyD88-deficient and wild-type mice to aerosolized Pseudomonas aeruginosa or S. aureus. As predicted, MyD88-deficient mice failed to mount an early cytokine or inflammatory response or to control bacterial replication after infection with P. aeruginosa, which resulted in necrotizing pneumonia and death. By contrast, MyD88-deficient mice controlled S. aureus infection despite blunted local cytokine and inflammatory responses. Thus, whereas MyD88-dependent signaling is integral to the initiation of cytokine and inflammatory responses to both pathogens following infection of the lower respiratory tract, MyD88 is essential for innate immunity to P. aeruginosa but not S. aureus.