Toll-like receptor 4 mediates innate immune responses to Haemophilus influenzae infection in mouse lung
Toll-like receptor 4 mediates innate immune responses to Haemophilus influenzae infection in mouse lung
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DOI：
10.4049/jimmunol.168.2.810
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发表时间：
2002-01-15
影响因子：
4.4
通讯作者：
Wilson, JM
中科院分区：
文献类型：
--
作者：
Wang, XR;Moser, C;Wilson, JM
Toll样受体(TLRs)参与调节宿主对微生物AGS的反应。本研究探讨了TLR4在小鼠肺内注射流感嗜血杆菌引起的先天免疫反应中的作用。两个不同品系的小鼠有效地清除了雾化的流感嗜血杆菌，同时在支气管肺泡灌洗中迅速产生了IL-1β、IL-6、TNF-α、巨噬细胞炎症蛋白(MIP)-1α和MIP-2，并相应地动员了肺内中性粒细胞。TLR4基因缺陷小鼠的同源品系在清除流感嗜血杆菌方面表现出显著的延迟，在支气管肺泡灌洗液中IL-1β、IL-6、TNF-α、MIP-1α和MIP-2显著减少，肺内中性粒细胞显著缺失。在表达TLR4的动物中，而不是TLR4缺乏的动物中，在流感嗜血杆菌感染后，传导气道上皮细胞中TNF-α和MIP-1α的表达上调，在此之前，基于1kappaB总体减少和磷酸化形式增加的发现，这些细胞中的NF-kappaB通路明显激活。这项研究证明了TLR4在介导肺部对流感嗜血杆菌的有效先天免疫反应中的关键作用。这表明呼吸道上皮细胞可能参与了流感嗜血杆菌感染的感知和先天免疫反应的信号传递。
Toll-like receptors (TLRs) have been implicated in the regulation of host responses to microbial Ags. This study characterizes the role of TLR4 in the innate immune response to intrapulmonary administration of Haemophilus influenzae in the mouse. Two different strains of mice efficiently cleared aerosolized H. influenzae concurrent with a brisk elaboration of IL-1beta, IL-6, TNF-alpha, macrophage-inflammatory protein (MIP)-1alpha, and MIP-2 in bronchoalveolar lavage and a corresponding mobilization of intrapulmonary neutrophils. Congenic strains of mice deficient in TLR4 demonstrated a substantial delay in clearance of H. influenzae with diminished IL-1beta, IL-6, TNF-alpha, MIP-1alpha, and MIP-2 in bronchoalveolar lavage and a notable absence of intrapulmonary neutrophils. In TLR4-expressing animals, but not TLR4-deficient animals, TNF-alpha and MIP-1alpha expression was up-regulated in epithelial cells of the conducting airway in response to H. influenzae which was preceded by an apparent activation of the NF-kappaB pathway in these cells based on the findings of decreased overall 1kappaB and an increase in its phosphorylated form. This study demonstrates a critical role of TLR4 in mediating an effective innate immune response to H. influenzae in the lung. This suggests that the airway epithelia might contribute to sensing of H. influenzae infection and signaling the innate immune response.