Paiva Ligia Almeida, Brand Camila, Bandeira-Melo Christianne, Bozza Patricia Torres, El-Cheikh Marcia Cury, Silva Patricia Martins, Borojevic Radovan, Perez Sandra Aurora Chavez
Laboratory of Immunopharmacology, Institute Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Parasit Vectors. 2015 Nov 9;8:577. doi: 10.1186/s13071-015-1197-3.
Hepatic myofibroblasts are relevant for pathogenesis of S. mansoni infection. In normal liver, these perisinusoidal cells are quiescent, express the lipocyte phenotype, and are located in the Disse's space, being the major site of vitamin A storage. When activated, they convert to myofibroblasts and contribute to granulomatous and diffuse liver fibrosis. In the present work, we observed that myofibroblasts obtained from granulomatous periovular inflammatory reactions in schistosome-infected mice (GR-MF) produce in vitro immunomodulatory cytokines for eosinophil activation: IL-5 and eotaxin.
The secretory activity of GR-MF was detected after TGF-β and IL-13 stimulation using 2D and 3D cell culture systems. In a mixed co-culture system using GR-MF with hematopoietic bone marrow cells from infected mice, we observed eosinophil survival that was dependent upon IL-5 and eotaxin, since antibodies against this cytokines decreased eosinophil population, as measured by eosinophil peroxidase activity.
These results indicate that GR-MF may contribute to maintenance of local eosinophilia in schistosomal hepatic granulomas, and can function as immunoregulatory cells, besides their role in production of fibrosis.
肝肌成纤维细胞与曼氏血吸虫感染的发病机制相关。在正常肝脏中,这些窦周细胞处于静止状态,表达脂肪细胞表型,位于狄氏间隙,是维生素A储存的主要部位。激活后,它们转变为肌成纤维细胞,并导致肉芽肿性和弥漫性肝纤维化。在本研究中,我们观察到从感染血吸虫的小鼠肉芽肿性卵周炎症反应中获得的肌成纤维细胞(GR-MF)在体外产生用于嗜酸性粒细胞激活的免疫调节细胞因子:白细胞介素-5(IL-5)和嗜酸性粒细胞趋化因子。
使用二维和三维细胞培养系统,在转化生长因子-β(TGF-β)和白细胞介素-13刺激后检测GR-MF的分泌活性。在使用GR-MF与感染小鼠造血骨髓细胞的混合共培养系统中,我们观察到嗜酸性粒细胞的存活依赖于IL-5和嗜酸性粒细胞趋化因子,因为针对这些细胞因子的抗体减少了嗜酸性粒细胞数量,这通过嗜酸性粒细胞过氧化物酶活性来衡量。
这些结果表明,GR-MF可能有助于维持血吸虫性肝肉芽肿中的局部嗜酸性粒细胞增多,并且除了在纤维化产生中的作用外,还可作为免疫调节细胞发挥作用。