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首页> 美国卫生研究院文献>Infection and Immunity >The Role of CD1d-Restricted NKT Cells in the Clearance of Pseudomonas aeruginosa from the Lung Is Dependent on the Host Genetic Background
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The Role of CD1d-Restricted NKT Cells in the Clearance of Pseudomonas aeruginosa from the Lung Is Dependent on the Host Genetic Background

机译：CD1d限制的NKT细胞在铜绿假单胞菌清除肺中的作用取决于宿主的遗传背景

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Pseudomonas aeruginosa is an important human opportunistic pathogen, accounting for a significant fraction of hospital-acquired lung infections. CD1d-restricted NKT cells comprise an unusual innate-like T cell subset that plays important roles in both bacterial and viral infections. Previous reports have differed in their conclusions regarding the role of NKT cells in clearance of P. aeruginosa from the lung. Since there is significant strain-dependent variation in NKT cell number and function among different inbred strains of mice, we investigated whether the role of NKT cells was dependent on the host genetic background. We found that NKT cells did indeed play a critical role in the clearance of P. aeruginosa from the lungs of BALB/c mice but that they played no discernible role in clearance from the lungs of C57BL/6 mice. We found that the strain-dependent role of NKT cells was associated with significant strain-dependent differences in cytokine production by lung NKT cells and that impaired clearance of P. aeruginosa in BALB/c CD1d−/− mice was associated with an increase in neutrophil influx to the lung and increased levels of proinflammatory cytokines and chemokines after infection. Finally, we found that the role of alveolar macrophages was also dependent on the genetic background. These data provide further support for a model in which the unusually high level of variability in NKT cell number and function among different genetic backgrounds may be an important contributor to infectious-disease susceptibility and pathology.
机译：铜绿假单胞菌是一种重要的人类机会性病原体，占医院获得性肺部感染的很大一部分。 CD1d限制的NKT细胞包含一个不寻常的先天性T细胞亚群，在细菌和病毒感染中都起着重要作用。关于NKT细胞在从肺部清除铜绿假单胞菌中的作用，以前的报道结论不同。由于不同自交系小鼠之间NKT细胞数量和功能存在明显的应变依赖性变化，因此我们研究了NKT细胞的作用是否取决于宿主的遗传背景。我们发现，NKT细胞确实在从BALB / c小鼠的肺中清除铜绿假单胞菌中起着关键作用，但是在从C57BL / 6小鼠的肺中清除中没有明显的作用。我们发现NKT细胞的应变依赖性作用与肺NKT细胞产生的细胞因子产生显着的应变依赖性差异有关，并且损害了BALB / c CD1d -/-小鼠中铜绿假单胞菌的清除率与感染后肺中性粒细胞流入增加以及促炎性细胞因子和趋化因子水平升高有关。最后，我们发现肺泡巨噬细胞的作用还取决于遗传背景。这些数据为以下模型提供了进一步的支持：在该模型中，不同遗传背景中NKT细胞数量和功能的异常高水平变异可能是传染病易感性和病理的重要因素。

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