Käser T, Pasternak J A, Delgado-Ortega M, Hamonic G, Lai K, Erickson J, Walker S, Dillon J R, Gerdts V, Meurens F
Vaccine and Infectious Disease Organization - International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, 120 Veterinary Road, S7N 5E3 Saskatoon, Saskatchewan, Canada; Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, 27607 Raleigh, NC, USA.
Vaccine and Infectious Disease Organization - International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, 120 Veterinary Road, S7N 5E3 Saskatoon, Saskatchewan, Canada.
Vaccine. 2017 Jan 3;35(1):91-100. doi: 10.1016/j.vaccine.2016.11.050. Epub 2016 Nov 25.
Chlamydia trachomatis infections are the most prominent bacterial sexually-transmitted disease world-wide and a lot of effort is put into the development of an effective vaccine. Pigs have been shown to be a valuable animal model for C. trachomatis vaccine development. The aim of this study was to decipher the T-cell-mediated immune response to chlamydial infections including C. trachomatis and C. suis, the chlamydia species naturally infecting pigs with a demonstrated zoonotic potential. Vaginal infection of pigs with C. suis and C. trachomatis lasted from 3 to 21days and intra-uterine infection was still present after 21days in 3 out of 5 C. suis- and 4 out of 5 C. trachomatis-inoculated animals and caused severe pathological changes. Humoral immune responses including neutralizing antibodies were found predominantly in response to C. suis starting at 14days post inoculation. The T-cell-mediated immune responses to C. trachomatis and C. suis-infections started at 7days post inoculation and consisted mainly of CD4 T cells which were either IFN-γ single cytokine-producing or IFN-γ/TNF-α double cytokine-producing T-helper 1 cells. IL-17-producing CD4 T cells were rare or completely absent. The T-cell-mediated immune responses were triggered by both homologous or heterologous re-stimulation indicating that cross-protection between the two chlamydia species is possible. Thus, having access to a working genital C. suis and C. trachomatis infection model, efficient monitoring of the host-pathogen interactions, and being able to accurately assess the responses to infection makes the pig an excellent animal model for vaccine development which also could bridge the gap to the clinical phase for C. trachomatis vaccine research.
沙眼衣原体感染是全球最主要的细菌性性传播疾病,人们为开发有效的疫苗付出了诸多努力。猪已被证明是沙眼衣原体疫苗研发的宝贵动物模型。本研究的目的是解析针对包括沙眼衣原体和猪衣原体在内的衣原体感染的T细胞介导的免疫反应,猪衣原体是自然感染猪且具有人畜共患病潜力的衣原体物种。用猪衣原体和沙眼衣原体对猪进行阴道感染持续3至21天,在5只接种猪衣原体的动物中有3只、5只接种沙眼衣原体的动物中有4只在21天后子宫内仍存在感染,并导致严重的病理变化。体液免疫反应包括中和抗体,主要在接种后14天开始出现,针对猪衣原体。对沙眼衣原体和猪衣原体感染的T细胞介导的免疫反应在接种后7天开始,主要由CD4 T细胞组成,这些细胞要么是产生单一细胞因子IFN-γ的T辅助细胞,要么是产生IFN-γ/TNF-α双细胞因子的T辅助1细胞。产生IL-17的CD4 T细胞很少或完全不存在。同源或异源再刺激均可触发T细胞介导的免疫反应,这表明两种衣原体物种之间可能存在交叉保护。因此,拥有一个有效的猪生殖道猪衣原体和沙眼衣原体感染模型、能够有效监测宿主-病原体相互作用以及能够准确评估对感染的反应,使得猪成为疫苗研发的优秀动物模型,这也可以弥合沙眼衣原体疫苗研究与临床阶段之间的差距。