Institute of Immunology, Genetics, and Metabolism, Jose de San Martin Clinical Hospital, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Biotechnology Research Institute, Technology Institute of Chascomús, National University of San Martin National Scientific and Technical Research, Buenos Aires, Argentina.
Am J Pathol. 2013 Dec;183(6):1918-1927. doi: 10.1016/j.ajpath.2013.08.006. Epub 2013 Oct 7.
In patients with active brucellosis, the liver is frequently affected by histopathologic lesions, such as granulomas, inflammatory infiltrations, and parenchymal necrosis. Herein, we examine some potential mechanisms of liver damage in brucellosis. We demonstrate that Brucella abortus infection inhibits matrix metalloproteinase-9 (MMP-9) secretion and induces collagen deposition and tissue inhibitor of matrix metalloproteinase-1 secretion induced by hepatic stellate cells (LX-2). These phenomena depend on transforming growth factor-β1 induction. In contrast, supernatants from B. abortus-infected hepatocytes and monocytes induce MMP-9 secretion and inhibit collagen deposition in hepatic stellate cells. Yet, if LX-2 cells are infected with B. abortus, the capacity of supernatants from B. abortus-infected hepatocytes and monocytes to induce MMP-9 secretion and inhibit collagen deposition is abrogated. These results indicate that depending on the balance between interacting cells and cytokines of the surrounding milieu, the response of LX-2 cells could be turned into an inflammatory or fibrogenic phenotype. Livers from mice infected with B. abortus displayed a fibrogenic phenotype with patches of collagen deposition and transforming growth factor-β1 induction. This study provides potential mechanisms of liver immune response induced by B. abortus-infected hepatic stellate cells. In addition, these results demonstrate that the cross talk of these cells with hepatocytes and macrophages implements a series of interactions that may contribute to explaining some of mechanisms of liver damage observed in human brucellosis.
在活动性布氏杆菌病患者中，肝脏常受到组织病理学病变的影响，如肉芽肿、炎症浸润和实质坏死。在此，我们研究了布氏杆菌病中肝脏损伤的一些潜在机制。我们证明布鲁氏菌流产感染抑制基质金属蛋白酶-9（MMP-9）的分泌，并诱导肝星状细胞（LX-2）诱导的胶原沉积和基质金属蛋白酶组织抑制剂-1 的分泌。这些现象取决于转化生长因子-β1 的诱导。相比之下，来自布鲁氏菌流产感染的肝细胞和单核细胞的上清液诱导 MMP-9 的分泌，并抑制肝星状细胞中的胶原沉积。然而，如果 LX-2 细胞被布鲁氏菌流产感染，来自布鲁氏菌流产感染的肝细胞和单核细胞上清液诱导 MMP-9 分泌和抑制胶原沉积的能力被削弱。这些结果表明，取决于相互作用的细胞和周围环境细胞因子之间的平衡，LX-2 细胞的反应可能转化为炎症或纤维发生表型。感染布鲁氏菌流产的小鼠肝脏显示出纤维发生表型，伴有胶原沉积和转化生长因子-β1 的诱导。本研究为布鲁氏菌感染的肝星状细胞诱导的肝脏免疫反应提供了潜在的机制。此外，这些结果表明，这些细胞与肝细胞和巨噬细胞的相互作用实施了一系列相互作用，可能有助于解释人类布氏杆菌病中观察到的一些肝脏损伤机制。
