Monocyte chemoattractant protein-1-dependent increase of Vα14 NKT cells in lungs and their roles in Th1 response and host defense in cryptococcal infection
Monocyte chemoattractant protein-1-dependent increase of Vα14 NKT cells in lungs and their roles in Th1 response and host defense in cryptococcal infection
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DOI：
10.4049/jimmunol.167.11.6525
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发表时间：
2001-12-01
影响因子：
4.4
通讯作者：
Saito, A
中科院分区：
文献类型：
--
作者：
Kawakami, K;Kinjo, Y;Saito, A
为了阐明 NKT 细胞在宿主防御隐球菌感染中的作用，我们检查了新生隐球菌气管内感染后肺部中这些细胞的比例（通过 CD3 和 NK1.1 的表达来鉴定）。该群体在感染后第 3 天增加，在第 6-7 天达到峰值，此后减少。在 V α 14 NKT 细胞缺陷小鼠中，这种增加显着减弱。通过与加载α-半乳糖神经酰胺的CD1d四聚体结合检测到的Va14 NKT细胞的比例以及Vα14 mRNA的表达在感染后以相似的动力学增加。与对照小鼠相比，V α 14 NKT 细胞缺陷小鼠的迟发型超敏反应和真菌特异性 Th1 细胞的分化减少。此外，在 V α 14 NKT 细胞缺陷小鼠中，从肺部消除这种真菌病原体的时间明显延迟。在 mRNA 和蛋白质水平上检测到，肺部单核细胞趋化蛋白 (MCP)-1 的产生在第 1 天增加，在第 3 天达到峰值水平，此后减少，先于 NKT 细胞增加。最后，在MCP-1缺陷小鼠中，感染后NKT细胞总数和Vα14(+)子集的增加显着减少。 Oar结果表明，NKT细胞，特别是V α 14(+)亚群，在感染新型隐球菌后以MCP-1依赖性方式在肺部积聚，并在Th1反应和宿主对该真菌病原体的抵抗力的发展中发挥重要作用。
To elucidate the role of NKT cells in the host defense to cryptococcal infection, we examined the proportion of these cells, identified by the expression of CD3 and NK1.1, in lungs after intratracheal infection with Cryptococcus neoformans. This population increased on day 3 after infection, reached a peak level on days 6-7, and decreased thereafter. In V alpha 14 NKT cell-deficient mice, such increase was significantly attenuated. The proportion of Va14 NKT cells, detected by binding to alpha -galactosylceramide-loaded CD1d tetramer, and the expression of V alpha 14 mRNA increased after infection with a similar kinetics. The delayed-type hypersensitivity response and differentiation of the fungus-specific Th1 cells was reduced in V alpha 14 NKT cell-deficient mice, compared with control mice. Additionally, elimination of this fungal pathogen from lungs was significantly delayed in V alpha 14 NKT cell-deficient mice. Production of monocyte chemoattractant protein (MCP)-1 in lungs, detected at both mRNA and protein levels, increased on day 1, reached a peak level on day 3, and decreased thereafter, which preceded the increase in NKT cells. Finally, the increase of total and V alpha 14(+) subset of NKT cells after infection was significantly reduced in MCP-1-deficient mice. Oar results demonstrated that NKT cells, especially V alpha 14(+) subset, accumulated in a MCP-1-dependent manner in the lungs after infection with C. neoformans and played an important role in the development of Th1 response and host resistance to this fungal pathogen.