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NK cells modulate T cell responses via interaction with dendritic cells in Chlamydophila pneumoniae infection.
Cellular Immunology ( IF 4.3 ) Pub Date : 2020-05-16 , DOI: 10.1016/j.cellimm.2020.104132
Lei Zhao 1 , Hong Wang 2 , Rony Thomas 3 , Xiaoling Gao 3 , Hong Bai 3 , Sudhanshu Shekhar 3 , Shuhe Wang 3 , Jie Yang 3 , Weiming Zhao 2 , Xi Yang 3
Affiliation  

Protective immune response to chlamydial infection is largely dependent on cell-mediated immune responses with IFN-γ production. Recent studies have shown the critical role of NK cells in bridging innate and adaptive immune responses. In this study, we investigated the effect of NK cells on T cell responses during Chlamydophila pneumoniae (Cpn) lung infection. The results showed that NK cells play a protective role in Cpn infection and influence T cell immunity largely though modulating dendritic cells (DCs) function. Specifically, we found that NK depletion significantly impaired type 1 T cell responses, but enhanced FOXP3+Treg cells and IL-10-producing CD4+T cells. The alteration of T cell responses was associated with more disease severity and higher chlamydial growth in the lung. Further analysis of DC phenotype and cytokine profile found that DCs from NK cell-depleted mice expressed lower levels of co-stimulatory molecules and produced higher levels of IL-10 than those from control IgG-treated mice. More importantly, the adoptive transfer of DCs from NK cell-depleted mice induced a much lower degree of type 1 T cell responses but a higher amount of FOXP3+ Treg cells and IL-10-producing CD4+T cells in the recipient mice than DCs from IgG-treated mice. In contrast to the strong protective effect observed in recipients of DCs from IgG-treated mice, the recipients of DCs from NK cell-depleted mice failed to be protected against Cpn infection. The data suggest that NK cells play a critical role in coordinating innate and adaptive immunity in Cpn lung infection by modulating the DC function to influence T cell responses.

中文翻译:

NK细胞通过与肺炎衣原体感染中的树突状细胞相互作用来调节T细胞反应。

对衣原体感染的保护性免疫应答在很大程度上取决于细胞介导的产生IFN-γ的免疫应答。最近的研究表明,NK细胞在桥接先天性和适应性免疫反应中起着关键作用。在这项研究中,我们调查了NK细胞对肺炎衣原体(Cpn)肺部感染期间T细胞反应的影响。结果表明,NK细胞通过调节树突状细胞(DCs)的功能,在Cpn感染中起保护作用,并极大地影响T细胞免疫。具体而言,我们发现NK耗竭明显损害1型T细胞反应,但增强了FOXP3 + Treg细胞和产生IL-10的CD4 + T细胞。T细胞反应的改变与更多的疾病严重程度和更高的肺衣原体生长相关。对DC表型和细胞因子谱的进一步分析发现,与来自对照IgG处理的小鼠相比,来自NK细胞耗尽的小鼠的DC表达较低水平的共刺激分子并产生较高水平的IL-10。更重要的是,来自耗竭NK细胞的小鼠的DC的过继转移引起的1型T细胞反应程度要低得多,但与来自小鼠的DC相比,受体小鼠中的FOXP3 + Treg细胞和产生IL-10的CD4 + T细胞数量更多IgG处理的小鼠。与在接受IgG处理的小鼠的DC的受体中观察到的强保护作用相反,来自NK细胞耗尽的小鼠的DC的受体未能针对Cpn感染进行保护。数据表明,NK细胞通过调节DC功能影响T细胞反应,在协调Cpn肺部感染的先天性和适应性免疫中起关键作用。
更新日期:2020-05-16
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