Dendritic cells pulsed with live and dead Legionella pneumophila elicit distinct immune responses
Dendritic cells pulsed with live and dead Legionella pneumophila elicit distinct immune responses
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DOI：
10.4049/jimmunol.172.3.1727
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发表时间：
2004-02-01
影响因子：
4.4
通讯作者：
Nukiwa, T
中科院分区：
文献类型：
--
作者：
Kikuchi, T;Kobayashi, T;Nukiwa, T
嗜肺军团菌是引起以严重肺炎为特征的军团病的病原体。在军团菌感染的病理生理学方面，巨噬细胞等炎性吞噬细胞的作用已有很好的文献报道，但树突状细胞(DC)的参与尚不清楚。在这项研究中，我们研究了树突状细胞在体外和体内接触嗜肺乳杆菌后产生的免疫反应。热灭活和福尔马林灭活的嗜肺乳杆菌诱导未成熟DC经历相似的表型成熟，但分泌的促炎细胞因子呈现不同的模式。灭活或福尔马林灭活嗜肺乳杆菌的DC成熟机制至少部分依赖于Toll样受体4信号或军团菌内毒素。在转移到幼鼠后，致死军团菌冲击的树突状细胞产生针对军团菌的血清Ig同型反应，导致保护性免疫，以抵御嗜肺乳杆菌对其他致命的呼吸道攻击。体内免疫反应需要树突状细胞的抗原提呈，尤其是MHC-II类分子上的抗原提呈，这种免疫产生了临床株和环境株之间的交叉保护。尽管活军团菌抑制了DC的成熟，但巨噬细胞对活的嗜肺乳杆菌和死亡的嗜肺乳杆菌一样被激活，MHC II类分子的上调证明了这一点。最后，DC，而不是巨噬细胞，对活的嗜肺乳杆菌表现出与其细胞周期进程一致的增殖反应。这些发现有助于更好地理解树突状细胞在军团菌感染获得性免疫中的作用。
Legionella pneumophila is the causative pathogen of Legionnaires' disease, which is characterized by severe pneumonia. In regard to the pathophysiology of Legionella infection, the role of inflammatory phagocytes such as macrophages has been well documented, but the involvement of dendritic cells (DCs) has not been clarified. In this study, we have investigated the immune responses that DCs generate in vitro and in vivo after contact with L. pneumophila. Heat- and formalin-killed L. pneumophila, but not live L. pneumophilia, induced immature DCs to undergo similar phenotypic maturation, but the secreted proinflammatory cytokines showed different patterns. The mechanisms of the DC maturation by beat- or formalin-killed L. pneumophila depended, at least in part, on Toll-like receptor 4 signaling or on Legionella LPS, respectively. After transfer to naive mice, DCs pulsed with dead Legionella produced serum Ig isotype responses specific for Legionella, leading to protective immunity against an otherwise lethal respiratory challenge with L. pneumophila. The in vivo immune responses required the Ag presentation of DCs, especially that on MHC class II molecules, and the immunity yielded cross-protection between clinical and environmental strains of L. pneumophila. Although the DC maturation was impaired by live Legionella, macrophages were activated toy live as well as dead L. pneumophila, as evidenced by the up-regulation of MHC class II. Finally, DCs, but not macrophages, exhibited a proliferative response to live L. pneumophila that was consistent with their cell cycle progression. These findings provide 2 better understanding of the role of DCs in adaptive immunity to Legionella infection.