Bilenki Laura, Wang Shuhe, Yang Jie, Fan Yijun, Jiao Lei, Joyee Antony George, Han Xiaobing, Yang Xi
Laboratory for Infection and Immunity, Departments of Immunology and Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
J Immunol. 2006 Nov 15;177(10):7067-75. doi: 10.4049/jimmunol.177.10.7067.
Chlamydial infections are serious public health concerns worldwide. In this study, we examined the role of dendritic cell (DC) subsets in inducing protective immunity against chlamydial infection using an adoptive transfer approach. We found that CD11c+CD8alpha+ (double-positive, DP) DC, compared with CD11c+CD8alpha- (single-positive, SP) DC isolated from infected mice, are more potent inducers of protective immunity. Specifically, mice pretreated with DPDC from infected mice, upon infection with Chlamydia trachomatis mouse pneumonitis (MoPn), experienced significantly less severe body weight loss and in vivo chlamydial growth. Analysis of MoPn-driven cytokine production by immune cells revealed that mice that were treated with DPDC produced significantly higher levels of Th1 (TNF-alpha, IFN-gamma, and IL-12) but lower levels of Th2 (IL-4, IL-5, and IL-13)-related cytokines than the recipients of SPDC following infection challenge. Moreover, DPDC-treated mice displayed significantly higher levels of MoPn-specific IgG2a production and delayed-type hypersensitivity responses compared with SPDC-treated mice. Furthermore, DPDC isolated from infected mice produced higher amounts of IL-12 and IL-10 in vitro in comparison with SPDC. These data indicate that CD8alpha+ DC have a significantly higher capacity in inducing protective immunity compared with CD8alpha- DC, demonstrating the crucial role of DC1-like cells in eliciting protection against C. trachomatis infection.
衣原体感染是全球严重的公共卫生问题。在本研究中,我们采用过继转移方法研究了树突状细胞(DC)亚群在诱导抗衣原体感染保护性免疫中的作用。我们发现,与从感染小鼠分离的CD11c + CD8α-(单阳性,SP)DC相比,CD11c + CD8α+(双阳性,DP)DC是更强的保护性免疫诱导剂。具体而言,用来自感染小鼠的DPDC预处理的小鼠,在感染沙眼衣原体小鼠肺炎(MoPn)后,体重减轻明显较轻,体内衣原体生长也较少。对免疫细胞产生的MoPn驱动的细胞因子分析显示,用DPDC处理的小鼠产生的Th1(TNF-α、IFN-γ和IL-12)水平显著更高,但Th2(IL-4、IL-5和IL-13)相关细胞因子水平低于感染攻击后接受SPDC的小鼠。此外,与SPDC处理的小鼠相比,DPDC处理的小鼠显示出MoPn特异性IgG2a产生水平显著更高,以及迟发型超敏反应。此外,与SPDC相比,从感染小鼠分离的DPDC在体外产生更多的IL-12和IL-10。这些数据表明,与CD8α- DC相比,CD8α+ DC在诱导保护性免疫方面具有显著更高的能力,证明了DC1样细胞在引发抗沙眼衣原体感染保护中的关键作用。