Department of Biology, South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio San Antonio, TX, USA.
Front Immunol. 2011 Dec 8;2:73. doi: 10.3389/fimmu.2011.00073. eCollection 2011.
We have shown that immunization with soluble recombinant chlamydial protease-like activity factor (rCPAF) and a T helper 1 type adjuvant can induce significantly enhanced bacterial clearance and protection against Chlamydia-induced pathological sequelae in the genital tract. In this study, we investigated the use of bone marrow derived dendritic cells (BMDCs) pulsed ex vivo with rCPAF + CpG in an adoptive subcutaneous immunization for the ability to induce protective immunity against genital chlamydial infection. We found that BMDCs pulsed with rCPAF + CpG efficiently up-regulated the expression of activation markers CD86, CD80, CD40, and major histocompatibility complex class II (MHC II), and secreted interleukin-12, but not IL-10 and IL-4. Mice adoptively immunized with rCPAF + CpG-pulsed BMDCs or UV-EB + CpG-pulsed BMDCs produced elevated levels of antigen-specific IFN-γ and enhanced IgG1 and IgG2a antibodies. Moreover, mice immunized with rCPAF + CpG-pulsed BMDCs or UV-EB + CpG-pulsed BMDCs exhibited significantly reduced genital Chlamydia shedding, accelerated resolution of infection, and reduced oviduct pathology when compared to infected mock-immunized animals. These results suggest that adoptive subcutaneous immunization with ex vivo rCPAF-pulsed BMDCs is an effective approach, comparable to that induced by UV-EB-BMDCs, for inducing robust anti-Chlamydia immunity.
我们已经表明,用可溶性重组衣原体蛋白酶样活性因子(rCPAF)和辅助性 T 细胞 1 型佐剂进行免疫接种可以显著增强细菌清除率,并预防衣原体引起的生殖道病理性后遗症。在这项研究中,我们研究了用 rCPAF+CpG 体外冲击骨髓来源树突状细胞(BMDC),并将其用于过继性皮下免疫接种,以诱导针对生殖道衣原体感染的保护性免疫。我们发现,rCPAF+CpG 冲击的 BMDC 可有效上调激活标志物 CD86、CD80、CD40 和主要组织相容性复合体 II(MHC II)的表达,并分泌白细胞介素-12,但不分泌 IL-10 和 IL-4。用 rCPAF+CpG 冲击的 BMDC 或 UV-EB+CpG 冲击的 BMDC 过继免疫的小鼠产生了高水平的抗原特异性 IFN-γ,并增强了 IgG1 和 IgG2a 抗体。此外,与感染的模拟免疫动物相比,用 rCPAF+CpG 冲击的 BMDC 或 UV-EB+CpG 冲击的 BMDC 免疫的小鼠生殖道衣原体脱落减少,感染清除加快,输卵管病理学减轻。这些结果表明,用体外 rCPAF 冲击的 BMDC 进行过继性皮下免疫接种是一种有效的方法,可与 UV-EB-BMDC 诱导的方法相媲美,可诱导强大的抗衣原体免疫。