Inêz-Ferreira Tatiana Maria, Mendoza Leonel, Vilela Raquel, Andrade Hélida Monteiro de, Haddad João Paulo, Nunes Fernanda Freire Campos, Gondim Isabela Moreira, Guimarães Tânia Mara Pinto Dabés, de Toledo Vicente de Paulo Coelho Peixoto
Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan USA; Biomedical Laboratory Diagnostics, Michigan State University, East Lansing, Michigan USA.
Heliyon. 2017 Mar 30;3(3):e00278. doi: 10.1016/j.heliyon.2017.e00278. eCollection 2017 Mar.
immunomodulatory vaccine (PiV) has been tested in clinical and experimental pythiosis. Previous data showed that immunogens have the ability to switch the Th2 immune response, normally in place during pythiosis, to a curative Th1 response. Pythiosis cannot be reproduced in experimental rodents with the exception of rabbits, and thus thorough evaluation of PiV´s immunomodulatory properties has been limited by the lack of a compatible inbred mouse model. In this study, we took advantage of the murine BALB/c infection model, where infected mice produce a Th2 response, to evaluate the PiV Th2 to Th1 immunomodulatory potential. Twenty-one days following challenge with large cutaneous granulomas developed in control mice, consistent with the expected Th2 response. In contrast, -induced cutaneous lesions in PiV-immunized mice were minimal or absent. Flow cytometry analysis of spleen cells from mice immunized with PiV and subsequently challenged with displayed more CD4+ and CD8+ cells than the control group. Moreover, spleen cells from mice that were immunized with PiV then challenged with secreted high levels of IFN-γ, with a moderate IL-2, IL-4, and IL-10 mixed cytokine profile upon re-stimulation with PiV. Anti- IgG1 in immunized animals was present at low titers suggesting a minor immunological role for this Ig isotype in this model. Our preliminary data showed that BALB/c mice challenged with represent an attractive model in which to study PiV´s immunomodulatory properties.
免疫调节疫苗(PiV)已在临床和实验性腐皮病中进行了测试。先前的数据表明,免疫原能够将腐皮病期间通常存在的Th2免疫反应转变为具有治愈作用的Th1反应。除兔子外,实验性啮齿动物无法复制腐皮病,因此,由于缺乏合适的近交小鼠模型,对PiV免疫调节特性的全面评估受到了限制。在本研究中,我们利用小鼠BALB/c感染模型(感染的小鼠产生Th2反应)来评估PiV从Th2到Th1的免疫调节潜力。用 攻击21天后,对照小鼠出现了大的皮肤肉芽肿,这与预期的Th2反应一致。相比之下,PiV免疫小鼠中由 诱导的皮肤病变极少或不存在。对先用PiV免疫随后用 攻击的小鼠的脾细胞进行流式细胞术分析,结果显示CD4+和CD8+细胞比对照组更多。此外,先用PiV免疫然后用 攻击的小鼠的脾细胞在再次用PiV刺激后分泌高水平的IFN-γ,伴有中等水平的IL-2、IL-4和IL-10混合细胞因子谱。免疫动物中的抗IgG1滴度较低,表明该Ig同种型在该模型中的免疫作用较小。我们的初步数据表明,用 攻击的BALB/c小鼠是研究PiV免疫调节特性的一个有吸引力的模型。