Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas, Consejo Nacional de Investigaciones Científicas y Técnicas, Cordoba, Argentina.
Facultad de Ciencias de la Salud, Escuela de Medicina, Universidad Católica de Córdoba, Cordoba, Argentina.
Infect Immun. 2018 May 22;86(6). doi: 10.1128/IAI.00773-17. Print 2018 Jun.
Giardiasis is one of the most common human intestinal diseases worldwide. Several experimental animal models have been used to evaluate infections, with gerbils () being the most valuable model due to their high susceptibility to infection, abundant shedding of cysts, and pathophysiological alterations and signs of disease similar to those observed in humans. Here, we report cytokine and antibody profiles both during the course of infection in gerbils and after immunization with a novel oral vaccine comprising a mixture of purified variant-specific surface proteins (VSPs). Transcript levels of representative cytokines of different immune profiles as well as macro- and microtissue alterations were assessed in Peyer's patches, mesenteric lymph nodes, and spleens. During infection, cytokine responses showed a biphasic profile: an early induction of Th1 (gamma interferon [IFN-γ], interleukin-1β [IL-1β], IL-6, and tumor necrosis factor [TNF]), Th17 (IL-17), and Th2 (IL-4) cytokines, together with intestinal alterations typical of inflammation, followed by a shift toward a predominant Th2 (IL-5) response, likely associated with a counterregulatory mechanism. Conversely, immunization with an oral vaccine comprising the entire repertoire of VSPs specifically showed high levels of IL-17, IL-6, IL-4, and IL-5, without obvious signs of inflammation. Both immunized and infected animals developed local (intestinal secretory IgA [S-IgA]) and systemic (serum IgG) humoral immune responses against VSPs; however, only infected animals showed evident signs of giardiasis. This is the first comprehensive report of cytokine expression and anti- antibody production during infection and VSP vaccination in gerbils, a reliable model of the human disease.
贾第虫病是全球最常见的人类肠道疾病之一。已经使用了几种实验动物模型来评估感染，沙鼠（）是最有价值的模型，因为它们对感染高度敏感，大量排出囊，并且病理生理改变和疾病迹象与人类观察到的相似。在这里，我们报告了在感染过程中以及用新的口服疫苗免疫后沙鼠中的细胞因子和抗体谱，该疫苗由纯化的变异表面蛋白（VSP）混合物组成。在派尔集合淋巴结、肠系膜淋巴结和脾脏中评估了不同免疫谱的代表性细胞因子的转录水平以及宏观和微观组织改变。在感染过程中，细胞因子反应表现出双相谱：早期诱导 Th1（伽马干扰素[IFN-γ]、白细胞介素-1β[IL-1β]、IL-6 和肿瘤坏死因子[TNF]）、Th17（IL-17）和 Th2（IL-4）细胞因子，同时伴有典型的炎症性肠道改变，随后转向主要的 Th2（IL-5）反应，这可能与一种代偿性机制有关。相反，用包含整个 VSP 谱的口服疫苗免疫特异性地显示出高水平的 IL-17、IL-6、IL-4 和 IL-5，没有明显的炎症迹象。免疫和感染的动物均针对 VSP 产生了局部（肠道分泌型 IgA[S-IgA]）和全身性（血清 IgG）体液免疫反应；然而，只有感染的动物表现出明显的贾第虫病迹象。这是首次全面报告在沙鼠感染和 VSP 疫苗接种过程中的细胞因子表达和抗抗体产生情况，沙鼠是人类疾病的可靠模型。
