Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14040-903, Brazil.
Department of Morphology, Physiology and Basic Pathology, School of Dentistry of Ribeirão Preto USP, University of São Paulo, Ribeirão Preto, 14040-904, Brazil.
Parasit Vectors. 2019 Nov 9;12(1):532. doi: 10.1186/s13071-019-3787-y.
Trypanosoma cruzi is the causative agent of Chagas disease, which is endemic to subtropical and tropical Americas. The disease treatment remains partially ineffective, involving therapies directed to the parasite as well as palliative strategies for the clinical manifestations. Therefore, novel candidates for disease control are necessary. Additionally, strategies based on parasite inhibition via specific targets and application of compounds which improve the immune response against the disease is welcomed. Ghrelin is a peptide hormone pointed as a substance with important cardioprotective, vasodilatory, anti-apoptotic, anti-oxidative and immune modulatory functions. The aims of this study were to evaluate the immunomodulatory effects of ghrelin in male Wistar rats infected with the Y strain of T. cruzi.
In order to delineate an immune response against T. cruzi mediated by ghrelin, we evaluated the following parameters: quantification of blood and cardiac parasites; analysis of cell markers (CD3, CD8, NK, NKT, CD45RA, macrophage and RT1B); nitric oxide (NO) production; lymphoproliferation assays; splenocyte apoptosis; and INF-γ, IL-12 and IL-6 quantification in sera.
The animals infected with T. cruzi and supplemented with ghrelin demonstrated an upregulated pattern in macrophage and NO production, whereas an anti-inflammatory response was observed in T cells and cytokines. The low response against T. cruzi mediated by T cells probably contributed to a higher colonization of the cardiac tissue, when compared to infected groups. On the other side, the peptide decreased the inflammatory infiltration in cardiac tissue infected with T. cruzi.
Ghrelin demonstrated a dual function in animals infected with T. cruzi. Further studies, especially related to the decrease of cardiac tissue inflammation, are needed in order to determine the advantages of ghrelin supplementation in Chagas disease, mostly for populations from endemic areas.
克氏锥虫是恰加斯病的病原体,该病流行于亚热带和热带美洲。目前该病的治疗仍部分无效,包括针对寄生虫的治疗以及针对临床表现的姑息治疗策略。因此,有必要寻找新的疾病控制候选物。此外,基于特定靶点抑制寄生虫和应用增强针对疾病免疫反应的化合物的策略也受到欢迎。胃饥饿素是一种肽类激素,具有重要的心脏保护、血管舒张、抗凋亡、抗氧化和免疫调节功能。本研究旨在评估胃饥饿素对感染 T. cruzi Y 株的雄性 Wistar 大鼠的免疫调节作用。
为了阐明胃饥饿素介导的针对 T. cruzi 的免疫反应,我们评估了以下参数:血液和心脏寄生虫的定量;细胞标志物(CD3、CD8、NK、NKT、CD45RA、巨噬细胞和 RT1B)分析;一氧化氮(NO)产生;淋巴细胞增殖试验;脾细胞凋亡;以及血清中 IFN-γ、IL-12 和 IL-6 的定量。
感染 T. cruzi 并补充胃饥饿素的动物表现出巨噬细胞和 NO 产生的上调模式,而 T 细胞和细胞因子则表现出抗炎反应。与感染组相比,T 细胞对 T. cruzi 的低反应可能导致心脏组织的更高定植。另一方面,该肽减少了感染 T. cruzi 的心脏组织中的炎症浸润。
胃饥饿素在感染 T. cruzi 的动物中表现出双重功能。需要进一步研究,特别是与减少心脏组织炎症相关的研究,以确定胃饥饿素补充在恰加斯病中的优势,特别是对来自流行地区的人群。