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.

The liver is frequently affected in patients with active brucellosis. In the present study, we identified a virulence factor involved in the modulation of hepatic stellate cell function and consequent fibrosis during Brucella abortus infection. This study assessed the role of BPE005 protein from B. abortus in the fibrotic phenotype induced on hepatic stellate cells during B. abortus infection in vitro and in vivo. We demonstrated that the fibrotic phenotype induced by B. abortus on hepatic stellate (LX-2) cells was dependent on BPE005, a protein associated with the type IV secretion system (T4SS) VirB from B. abortus. Our results indicated that B. abortus inhibits matrix metalloproteinase 9 (MMP-9) secretion through the activity of the BPE005-secreted protein and induces concomitant collagen deposition by LX-2 cells. BPE005 is a small protein containing a cyclic nucleotide monophosphate binding domain (cNMP) that modulates the LX-2 cell phenotype through a mechanism that is dependent on the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway. Altogether, these results indicate that B. abortus tilts LX-2 cells to a profibrogenic phenotype employing a functional T4SS and the secreted BPE005 protein through a mechanism that involves the cAMP and PKA signaling pathway. Brucellosis is a worldwide zoonosis characterized by hepatomegaly, splenomegaly, and peripheral lymphadenopathy. It is a chronic and debilitating infection caused by Gram-negative facultative intracellular bacteria that infect domestic and wild animals and that can be transmitted to humans (1, 2). The frequency of liver involvement in active brucellosis ranges from 5% to 52% or more (1). However, although numerous studies have focused on brucellar liver histopathology (1), the pathogenic mechanisms of liver disease caused by Brucella have not been completely investigated at the molecular and cellular levels.Liver fibrosis is a wound-healing response to chronic hepatic injury, which may be caused by alcohol abuse, hepatitis virus infection, or nonalcoholic steatohepatitis, and it is characterized by an excessive accumulation of extracellular matrix proteins in the liver (3, 4). An early event in the development of liver fibrosis is the activation of hepatic stellate cells (HSCs), the major cell type responsible for increased synthesis of extracellular matrix proteins (5). An elevated level of transforming growth factor ␤1 (TGF-␤1) is also observed in the damaged liver, and it has a close correlation with fibrogenic changes in HSCs and liver tissue (6-8). In addition, decreased matrix metalloproteinase 9 (MMP-9) expression was observed in alcoholic liver fibrosis (9). This fibrogenic phenotype involves alterations in the balance of MMPs and their natural inhibitors-tissue inhibitors of metalloproteinases (TIMPs). In particular, MMP-2 and MMP-9 (gelatinase A and B, respectively) are important in regulating fibrogenesis and scar degradation. They can degrade a variety of collagens, including basement membrane (type IV collagen), denatured fibrillar...

In this work, we present the development of a point-of-care platform for the serologic diagnosis of infectious diseases. The complete system consists of magnetic particles with immobilized antigens, disposable electrochemical cells, hardware and software. The main purpose of this paper is to present the last two components. The platform is powered by a rechargeable battery and can be controlled using mobile devices, allowing point-of-care diagnosis of diseases. The platform was successfully tested for the diagnosis of foot-and-mouth disease, human and bovine brucellosis, and Chagas disease.