Controls for lung dendritic cell maturation and migration during respiratory viral infection
Controls for lung dendritic cell maturation and migration during respiratory viral infection
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DOI：
10.4049/jimmunol.179.3.1438
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发表时间：
2007-08-01
影响因子：
4.4
通讯作者：
Holtzman, Michael J.
中科院分区：
文献类型：
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作者：
Grayson, Mitchell H.;Ramos, Madeleine S.;Holtzman, Michael J.
树突状细胞非常适合协调对感染的先天和适应性免疫反应，但我们对这些细胞如何对常见呼吸道病毒感染作出反应知之甚少。副粘病毒感染是儿童严重呼吸道疾病的最常见原因，并与哮喘风险增加有关。因此，我们使用仙台病毒引发的高保真副粘病毒呼吸道感染小鼠模型来检测肺中常规和浆细胞样树突状细胞（分别为cdc和pDCs）的反应。我们发现pDCs在基线时很少，但在感染期间成为肺树突状细胞的主要群体。这种招募允许ifn - α在感染部位的局部来源。相比之下，cdc在病毒接种后2小时内迅速分化为髓系cdc，并开始从肺部迁移到引流淋巴结，这些事件导致肺部cdc数量迅速减少，并在病毒感染部位保持减少。肺cdc的成熟和迁移依赖于Ccl5和Ccr5信号，因为这些事件在Ccl5（-/-）和Ccr5（-/-）小鼠中明显受损。在Ccl5（-/-）或Ccr5（-/-）小鼠中，cDCs不能迁移到引流淋巴结与CCR7上调受损有关，而CCR7上调通常会指导这一过程。我们的研究结果表明，pDCs和cdc对呼吸道副粘病毒感染有明显的反应，其运动模式应该分别用于协调先天和适应性免疫反应。
Dendritic cells are ideally suited to orchestrate the innate and adaptive immune responses to infection, but we know little about how these cells respond to infection with common respiratory viruses. Paramyxoviral infections are the most frequent cause of serious respiratory illness in childhood and are associated with an increased risk of asthma. We therefore used a high-fidelity mouse model of paramyxoviral respiratory infection triggered by Sendai virus to examine the response of conventional and plasmacytoid dendritic cells (cDCs and pDCs, respectively) in the lung. We found that pDCs are scarce at baseline but become the predominant population of lung dendritic cells during infection. This recruitment allows for a source of IFN-alpha locally at the site of infection. In contrast, cDCs rapidly differentiate into myeloid cDCs and begin to migrate from the lung to draining lymph nodes within 2 h after viral inoculation, These events cause the number of lung cDCs to decrease rapidly and remain decreased at the site of viral infection. Maturation and migration of lung cDCs depends on Ccl5 and Ccr5 signals because these events are significantly impaired in Ccl5(-/-) and Ccr5(-/-) mice. cDCs failure to migrate to draining lymph nodes in Ccl5(-/-) or Ccr5(-/-) mice is associated with impaired up-regulation of CCR7 that would normally direct this process. Our results indicate that pDCs and cDCs respond distinctly to respiratory paramyxoviral infection with patterns of movement that should serve to coordinate the innate and adaptive immune responses, respectively.