Involvement of Fractalkine/CX3CL1 Expression by Dendritic Cells in the Enhancement of Host Immunity against Legionella pneumophila
Involvement of Fractalkine/CX3CL1 Expression by Dendritic Cells in the Enhancement of Host Immunity against Legionella pneumophila
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DOI：
10.1128/iai.73.9.5350-5357.2005
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发表时间：
2005-09
影响因子：
3.1
通讯作者：
T. Kikuchi;S. Andarini;H. Xin;K. Gomi;Y. Tokue;Y. Saijo;T. Honjo;A. Watanabe;T. Nukiwa
中科院分区：
文献类型：
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作者：
T. Kikuchi;S. Andarini;H. Xin;K. Gomi;Y. Tokue;Y. Saijo;T. Honjo;A. Watanabe;T. Nukiwa
军团病临床表现为由嗜肺军团菌引起的重症肺炎。然而，以树突状细胞（DC）为中心的宿主防御L。嗜肺性肺炎还没有被完全描述。在这项研究中，我们关注了一种有效的淋巴细胞化学引诱物，fractalkine/CX 3CL 1，并观察到当DC遇到L.嗜肺菌因此，我们假设由军团菌捕获DC表达的fractalkine参与诱导针对军团菌的T细胞介导的免疫应答，这将通过DC的遗传调节以过表达fractalkine来增强。体内免疫攻击实验表明，DC修饰的重组腺病毒载体过表达fractalkine（AdFKN）和脉冲与热灭活军团菌保护免疫小鼠免受致命的军团菌感染，体内保护性免疫的产生依赖于宿主淋巴细胞亚群，包括CD 4 + T细胞，CD 8 + T细胞，和B细胞。与此相一致，免疫与AdFKN/军团菌/DC诱导显着更高水平的血清抗军团菌抗体的几个同种型比那些诱导的对照免疫。免疫小鼠脾细胞的进一步分析表明，AdFKN/Legionella/DC免疫诱导了Th 1为主的抗军团菌免疫应答。嗜肺菌这些观察结果表明，fractalkine可能在DC介导的宿主防御细胞内病原体，如L。嗜肺菌
ABSTRACT Legionnaires' disease is clinically manifested as severe pneumonia caused by Legionella pneumophila. However, the dendritic cell (DC)-centered immunological framework of the host defense against L. pneumophila has not been fully delineated. For this study, we focused on a potent chemoattractant for lymphocytes, fractalkine/CX3CL1, and observed that the fractalkine expression of DCs was somewhat up-regulated when they encountered L. pneumophila. We therefore hypothesized that fractalkine expressed by Legionella-capturing DCs is involved in the induction of T-cell-mediated immune responses against Legionella, which would be enhanced by a genetic modulation of DCs to overexpress fractalkine. In vivo immunization-challenge experiments demonstrated that DCs modified with a recombinant adenovirus vector to overexpress fractalkine (AdFKN) and pulsed with heat-killed Legionella protected immunized mice from a lethal Legionella infection and that the generation of in vivo protective immunity depended on the host lymphocyte subsets, including CD4+ T cells, CD8+ T cells, and B cells. Consistent with this, immunization with AdFKN/Legionella/DC induced significantly higher levels of serum anti-Legionella antibodies of several isotypes than those induced by control immunizations. Further analysis of spleen cells from the immunized mice indicated that the AdFKN/Legionella/DC immunization elicited Th1-dominated immune responses to L. pneumophila. These observations suggest that fractalkine may play an important role in the DC-mediated host defense against intracellular pathogens such as L. pneumophila.