Depletion of NK cells results in disseminating lethal infection with Bordetella pertussis associated with a reduction of antigen-specific Th1 and enhancement of Th2, but not Tr1 cells
Depletion of NK cells results in disseminating lethal infection with Bordetella pertussis associated with a reduction of antigen-specific Th1 and enhancement of Th2, but not Tr1 cells
复制标题
DOI：
10.1002/eji.200425092
复制
发表时间：
2004-09-01
影响因子：
5.4
通讯作者：
Mills, KHG
中科院分区：
文献类型：
--
作者：
Byrne, P;McGuirk, P;Mills, KHG
ifn - γ在抵抗百日咳博德泰拉方面起着关键作用，但Th1细胞只有在感染开始消退后才能检测到，这表明先天ifn - γ在感染早期具有保护作用。在这里，我们证明了NK细胞和NKT细胞在百日咳呼吸攻击后进入肺部的显著募集。此外，在感染的急性阶段，NK细胞是肺中ifn - γ的主要来源。NK细胞对ifn - γ产生的刺激是间接通过百日咳b杆菌激活的树突状细胞产生IL-12或IL-23。用抗亚洲鱼神经节- n -四烷基神经酰胺抗体消耗NK细胞导致致命感染，肺部细菌负荷增加，细菌通过血液传播到肝脏。NK细胞缺失小鼠的百日咳特异性ifn - γ显著降低，IgG1和IL-5增强，但IL-10的产生不明显，这表明调节性T细胞与Th1细胞同时被诱导，但NK细胞缺失导致th2型反应增强。这些发现表明NK细胞通过激活il -12介导的ifn - γ的产生来赋予百日咳抗性，这增强了巨噬细胞的抗菌活性，但也促进了Th1细胞的分化。
IFN-gamma plays a critical role in protection against Bordetella pertussis, but Th1 cells are only detectable after the infection has started to resolve, suggesting a protective role for innate IFN-gamma early in infection. Here, we demonstrate significant recruitment of NK cells and NKT cells into the lungs following respiratory challenge with B. pertussis. Furthermore, NK cells are the primary source of IFN-gamma in the lungs during the acute stage of infection. Stimulation of IFN-gamma production by NK cells was indirect through B. pertussis-activated IL-12 or IL-23 production by dendritic cells. Depletion of NK cells with anti-asialo ganglio-N-tetraosylceramide antibody resulted in a lethal infection, with enhancement of bacterial load in the lungs and dissemination of the bacteria to the liver via the blood. NK cell-depleted mice had significantly reduced B. pertussis-specific IFN-gamma and enhanced IgG1 and IL-5, but not IL-10 production, suggesting that regulatory T cells are induced simultaneously with Th1 cells, but the absence of NK cells resulted in enhancement of Th2-type responses. These findings suggest that NK cells confer resistance to B. pertussis by activating IL-12-mediated production of IFN-gamma, which enhances the anti-bacterial activity of macrophages, but also promotes the differentiation of Th1 cells.