摘要
目的探索鼠衣原体(Cm)肺部感染中自然杀伤(NK)细胞调节Th17/Treg应答的作用机制。方法建立鼠Cm肺部感染模型,采用CD11c~+磁珠分选NK细胞去除鼠和同型对照抗体处理鼠的脾树突状细胞(DCs),转输至野生鼠体内,对应小鼠分为NK~-DCs组(n=13)和NK~+DCs组(n=13)。经Cm攻击感染后,比较两组小鼠疾病严重程度;流式细胞术分析脾和肺中Th17及Treg应答变化。结果与转输NK~+DCs小鼠相比,转输NK~-DCs的小鼠病情加重,表现为体质量下降、肺载菌量增加及病理损伤加重,同时脾和肺中Th17应答降低,Treg应答增强,Th17/Treg应答失衡,差异均有统计学意义。结论在Cm肺部感染中,NK细胞能够通过调控DCs有效启动Th17应答,抑制Treg应答,发挥抗感染免疫保护作用。
Objective To explore the mechanism of natural killer(NK) cells in regulating of Th17/Treg cell responses during chlamydia muridarum(Cm) lung infection. Methods A pulmonary infection model of Cm was established. The spleen dendritic cells(DCs) from Cm-infected mice with or without NK cells depletion were obtained by application of CD11 c~+ MicroBeads. The na?EF;ve mice were given intravenous injection of DCs from different groups of mice, and divided into NK~-DCs recipients group(n=13) and NK~+DCs recipients group(n=13). After adoptive transfer, the same infection method was used to recipient mice with Cm. The degree of disease was compared between the two groups. Flow cytometry was used to detect the changes of Th17 and Treg cells in the spleen and lung of mice. Results Compared with NK~+DCs recipients, NK~-DCs recipients exhibited aggravated disease, higher weight loss and severe lung injury. Immunological analysis showed the proportion of Th17 cells in spleen and lung was reduced while the proportion of Treg cell response was enhanced, which contributed to imbalance of Th17/Treg response in NK~-DCs recipients.Conclusion NK cells can effectively initiate Th17 cells response and inhibit Treg cell response by modulating DCs and thus play an important role in controlling chlamydial infection.
引文
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