Ramos Eliézer L P, Santana Silas S, Silva Murilo V, Santiago Fernanda M, Mineo Tiago W P, Mineo José R
Laboratório de Imunoparasitologia, Instituto de Ciências Biomédicas-Universidade Federal de Uberlândia Uberlândia, Brazil.
Front Cell Infect Microbiol. 2016 Nov 25;6:164. doi: 10.3389/fcimb.2016.00164. eCollection 2016.
Infection by affects around one-third of world population and the treatment for patients presenting toxoplasmosis clinically manifested disease is mainly based by a combination of sulfadiazine, pyrimethamine, and folinic acid. However, this therapeutic protocol is significantly toxic, causing relevant dose-related bone marrow damage. Thus, it is necessary to improve new approaches to investigate the usefulness of more effective and non-toxic agents for treatment of patients with toxoplasmosis. It has been described that lectins from plants can control parasite infections, when used as immunological adjuvants in vaccination procedures. This type of lectins, such as ArtinM and ScLL is able to induce immunostimulatory activities, including efficient immune response against parasites. The present study aimed to evaluate the potential immunostimulatory effect of ScLL and ArtinM for treatment of infection during acute phase, considering that there is no study in the literature accomplishing this issue. For this purpose, bone marrow-derived macrophages (BMDMs) were treated with different concentrations from each lectin to determine the maximum concentration without or with lowest cytotoxic effect. After, it was also measured the cytokine levels produced by these cells when stimulated by the selected concentrations of lectins. We found that ScLL showed high capacity to induce of pro-inflammatory cytokine production, while ArtinM was able to induce especially an anti-inflammatory cytokines production. Furthermore, both lectins were able to increase NO levels. Next, we evaluated the treatment effect of ScLL and ArtinM in C57BL/6 mice infected by ME49 strain from . The animals were infected and treated with ScLL, ArtinM, ArtinM plus ScLL, or sulfadiazine, and the following parameters analyzed: Cytokines production, brain parasite burden and survival rates. Our results demonstrated that the ScLL or ScLL plus ArtinM treatment induced production of pro-inflammatory and anti-inflammatory cytokines, showing differential but complementary profiles. Moreover, when compared with non-treated mice, the parasite burden was significantly lower and survival rates higher in mice treated with ScLL or ScLL plus ArtinM, similarly with sulfadiazine treatment. In conclusion, the results demonstrated the suitable potential immunotherapeutic effect of ScLL and ArtinM lectins to control acute toxoplasmosis in this experimental murine model.
由[病原体名称未提及]感染影响着全球约三分之一的人口,对于临床出现弓形虫病症状的患者,其治疗主要基于磺胺嘧啶、乙胺嘧啶和亚叶酸的联合使用。然而,这种治疗方案毒性显著,会造成与剂量相关的严重骨髓损伤。因此,有必要改进新方法,以研究更有效且无毒的药物治疗弓形虫病患者的有效性。据描述,植物凝集素在疫苗接种程序中用作免疫佐剂时,能够控制寄生虫感染。这类凝集素,如ArtinM和ScLL,能够诱导免疫刺激活性,包括对寄生虫产生有效的免疫反应。鉴于文献中尚无研究解决此问题,本研究旨在评估ScLL和ArtinM在急性期治疗[病原体名称未提及]感染时的潜在免疫刺激作用。为此,用不同浓度的每种凝集素处理骨髓来源的巨噬细胞(BMDMs),以确定无细胞毒性或细胞毒性最低时的最大浓度。之后,还测定了这些细胞在所选浓度的凝集素刺激下产生的细胞因子水平。我们发现ScLL具有诱导促炎细胞因子产生的高能力,而ArtinM尤其能够诱导抗炎细胞因子的产生。此外,两种凝集素都能够提高一氧化氮(NO)水平。接下来,我们评估了ScLL和ArtinM对感染[病原体名称未提及]ME49株的C57BL / 6小鼠的治疗效果。动物感染后用ScLL、ArtinM、ArtinM加ScLL或磺胺嘧啶进行治疗,并分析以下参数:细胞因子产生、脑内寄生虫负荷和存活率。我们的结果表明,ScLL或ScLL加ArtinM治疗可诱导促炎和抗炎细胞因子的产生,呈现出不同但互补的特征。此外,与未治疗的小鼠相比,用ScLL或ScLL加ArtinM治疗的小鼠寄生虫负荷显著降低,存活率更高,与磺胺嘧啶治疗相似。总之,结果表明ScLL和ArtinM凝集素在该实验小鼠模型中对控制急性弓形虫病具有合适的潜在免疫治疗效果。