Rodrigues-Alves M L, Melo-Júnior O A O, Coelho-Dos-Reis J G, Pascoal-Xavier M A, Alves-Costa H, Reis C A, Dutra W O, Silva R E, Senna M C R, Faria A C, Medeiros N I, Gomes J A S, Silveira-Lemos D, Martins-Filho O A, Teixeira-Carvalho A, Costa-Silva M F, Giunchetti R C, Peruhype-Magalhães V
Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Grupo Integrado de Pesquisa em Biomarcadores, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brazil.
Parasite Immunol. 2018 Aug;40(8):e12565. doi: 10.1111/pim.12565. Epub 2018 Jul 8.
Cutaneous leishmaniasis (CL) treatment is based on therapy with Glucantime , yet, there are few laboratory methods to monitor its success. In this study, ex vivo and in vitro evaluations of peripheral blood monocytes were performed in a longitudinal study to characterize the impact of Glucantime on overall phenotypic/functional features of these cells from CL patients to identify predictive biomarkers for post-therapeutic monitoring by flow cytometry. The ex vivo evaluation from CL patients demonstrated a modulatory profile before treatment, with a decrease in TLR-2, FcγRII, HLA-DR, CD86, IFN-γR, TNF, IL-12, NO, and an increase in FcγRIII and IL-10R. Conversely, treatment changes some of these biomarker expressions by decreasing FcγRIII and IL-10R and increasing IFN-γR, IL-12 and NO. Moreover, an in vitro analysis of these patients showed a reduced phagocytic capacity of Leishmania braziliensis and higher levels of IL-10 and TGF-β modulating functional profile. Regardless of the compromised L. braziliensis phagocytic capacity, treatment re-established the production of IL-12, IL-10, TGF-β and NO at the basal level. Notably, monocytes from patients with early cicatrization showed enhanced FcγRI and FcγRII expressions and reduced IL-10, which was further corroborated by a baseline fold change analysis. Finally, the logistic regression model emphasized the performance of FcγRI, FcγRII and IL-10 as robust predictive biomarkers for post-therapeutic cicatrization during cutaneous leishmaniasis.
皮肤利什曼病(CL)的治疗基于使用葡糖胺锑钠进行治疗,然而,几乎没有实验室方法来监测其治疗效果。在本研究中,我们进行了一项纵向研究,对外周血单核细胞进行了体外和体内评估,以表征葡糖胺锑钠对CL患者这些细胞的整体表型/功能特征的影响,从而通过流式细胞术识别用于治疗后监测的预测性生物标志物。对CL患者的体外评估显示,治疗前存在调节性特征,TLR-2、FcγRII、HLA-DR、CD86、IFN-γR、TNF、IL-12、NO减少,FcγRIII和IL-10R增加。相反,治疗通过降低FcγRIII和IL-10R以及增加IFN-γR、IL-12和NO改变了其中一些生物标志物的表达。此外,对这些患者的体外分析显示,巴西利什曼原虫的吞噬能力降低,IL-10和TGF-β水平升高,调节功能特征。尽管巴西利什曼原虫的吞噬能力受损,但治疗使IL-12、IL-10、TGF-β和NO的产生恢复到基础水平。值得注意的是,早期愈合患者的单核细胞显示FcγRI和FcγRII表达增强,IL-10减少,基线倍数变化分析进一步证实了这一点。最后,逻辑回归模型强调了FcγRI、FcγRII和IL-10作为皮肤利什曼病治疗后愈合的强大预测生物标志物的性能。