Modulation of pulmonary dendritic cell function during mycobacterial infection
Modulation of pulmonary dendritic cell function during mycobacterial infection
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DOI：
10.1128/iai.01079-07
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发表时间：
2008-02-01
影响因子：
3.1
通讯作者：
Boom, W. Henry
中科院分区：
文献类型：
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作者：
Anis, Mursalin M.;Fulton, Scott A.;Boom, W. Henry
我们之前已经报道过，在分枝杆菌感染期间，肺部的初始CD4(+)T细胞活化增强。探讨趋化因子受体CCR7及其配体在卡介苗(BCG)肺部感染时CD11c(+)肺树突状细胞(DCs)激活初始CD4(+)T细胞能力中的作用。卡介苗感染导致DC在肺内积聚和成熟，并随着分枝杆菌负荷的下降而持续。感染小鼠肺树突状细胞表达的主要组织相容性复合体II类(MHC-II)高于未感染小鼠。未感染和感染的小鼠肺树突状细胞上CCR7的表达水平相似。CCR7配体CCL19的基因表达在整个卡介苗感染过程中呈进行性增加，且其表达呈MyD88依赖性。卡介苗感染小鼠的CD11c(+)肺细胞比未感染小鼠的CD11c(+)肺细胞更能激活卵清蛋白(OVA)特异性的初始CD4(+)T细胞。有趣的是，在分枝杆菌感染高峰期，CD11c(Hi)MHchi肺树突状细胞对CCR7配体CCL21的趋化能力略有下降，在感染后期，当肺中几乎没有发现细菌时，激活初始CD4(+)T细胞的效率低于来自小鼠的树突状细胞。这些结果表明，在卡介苗感染过程中，炎症和CCL19的持续表达导致了DC在肺内的募集、激活和滞留，这些DC可以原位激活初始的CD4(+)T细胞。
We have previously reported that during mycobacterial infection, naive CD4(+) T-cell activation is enhanced in the lungs. We investigated the role of chemokine receptor CCR7 and its ligands in the ability of CD11c(+) lung dendritic cells (DCs) to activate naive CD4(+) T cells during pulmonary infection with Mycobacterium bovis bacillus Calmette-Guerin (BCG). BCG infection resulted in the accumulation and maturation in the lungs of DCs that persisted as the mycobacterial burden declined. Lung DCs from infected mice expressed more major histocompatibility complex class II (MHC-II) than those from uninfected mice. CCR7 expression levels on lung DCs were comparable among uninfected and infected mice. The gene expression of the CCR7 ligand CCL19 progressively increased throughout BCG infection, and its expression was MyD88 dependent. CD11c(+) lung cells from BCG-infected mice activated ovalbumin (OVA)-specific naive CD4(+) T cells more than CD11c(+) lung cells from uninfected mice. Interestingly, during peak mycobacterial infection, CD11c(hi) MHChi lung DCs had slightly decreased chemotaxis toward the CCR7 ligand CCL21 and less efficiency in activating naive CD4(+) T cells than DCs from mice during late-stage infection, when few bacilli are found in the lung. These findings suggest that during BCG infection, the inflammation and sustained expression of CCL19 result in the recruitment, activation, and retention in the lung of DCs that can activate naive CD4(+) T cells in situ.