Critical role of Vα14+ natural killer T cells in the innate phase of host protection against Streptococcus pneumoniae infection
Critical role of Vα14+ natural killer T cells in the innate phase of host protection against Streptococcus pneumoniae infection
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DOI：
10.1002/eji.200324254
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发表时间：
2003-12-01
影响因子：
5.4
通讯作者：
Saito, A
中科院分区：
文献类型：
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作者：
Kawakami, K;Yamamoto, N;Saito, A
本研究旨在使用缺乏该淋巴细胞亚群的Jalpha 281基因破坏小鼠（Jalpha 281 KO小鼠）来阐明Valpha 14（+）NKT细胞在宿主防御肺炎链球菌肺部感染中的作用。在这些小鼠中，肺炎球菌感染严重加剧，如与野生型（WT）小鼠相比存活时间更短和肺中活细菌显著增加所示。在S.肺炎感染。这种增加在具有单核细胞趋化蛋白（MCP）-1遗传破坏的小鼠中显著降低，MCP-1在WT小鼠感染的早期阶段产生。在Jalpha 281 KO小鼠的肺中，中性粒细胞的数量在12 h时显著低于WT小鼠。为了支持这一发现，与WT小鼠相比，Jalpha 281 KO小鼠中感染肺中的巨噬细胞炎性蛋白（MIP）-2和TNF-α的合成分别在3 h以及3 h和6 h时显著减少。此外，用α-GalCer治疗小鼠显著改善了这种感染的结果。我们的研究结果证实了MCP-1依赖的Valpha 14（+）NKT细胞的募集及其在早期宿主抗S.通过促进嗜中性粒细胞向感染部位的运输，可以抑制肺炎。
The present study was designed to elucidate the role of Valpha14(+) NKT cells in the host defense against pulmonary infection with Streptococcus pneumoniae using Jalpha281 gene-disrupted mice (Jalpha281KO mice) that lacked this lymphocyte subset. In these mice, pneumococcal infection was severely exacerbated, as shown by the shorter survival time and marked increase of live bacteria in the lung compared to wild-type (WT) mice. The proportion of Valpha14(+) NKT cells, detected by an alpha-galactosylceramide (alpha-GalCer)-loaded CD1d tetramer, increased in the lung after S. pneumoniae infection. This increase was significantly reduced in mice with a genetic disruption of monocyte chemotactic protein (MCP)-1, which was produced in the early phase of infection in WT mice. In the lungs of Jalpha281KO mice, the number of neutrophils was significantly lower at 12 h than that in WT mice. In support of this finding, macrophage inflammatory protein (MIP)-2 and TNF-alpha synthesis in infected lungs was significantly reduced at 3 h and at both 3 and 6 h, respectively, in Jalpha281KO mice, compared to WT mice. In addition, treatment of mice with alpha-GalCer significantly improved the outcome of this infection. Our results demonstrated MCP-1-dependent recruitment of Valpha14(+) NKT cells and their critical role in early host protection against S. pneumoniae by promoting the trafficking of neutrophils to the site of infection.