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.
The development of an inmunosensor for the point-of-care detection of the foot-and-mouth cattle disease is presented. The detector is based on an ELISA method with electrochemical detection. A non-structural protein, 3ABC, is used to selectively detect antibodies is used to selectively detect anti-3ABC antibodies produced after infection. The biological test is performed onto a screen printed electrodes. A dedicated small, portable potentiostat is employed for the control of the sensors, as well as data acquisition, processing, and storage.
Usutu disease, was issued in 2016, in order to develop a network between human and veterinary surveillance. In September 2016, a human case of neuroinvasive WND, with symptoms of encephalitis and meningitis, was confirmed in a 38-year-old man from Trapani, by serological evaluation on serum and liquor. The subject, recovered from illness, referred to have spent his holiday in Santo Domingo in August 2016. The authors describe the application of the integrated plan in this human WND case.Methods & Materials: According to the surveillance plan, sera and blood samples from 11 horses, 271 chickens and two dogs were collected around the residency of the human clinical case. The entomological monitoring was performed on mosquitos collected in 8 selected sites, within 1 km from the same residency. IgM and IgG ELISA assays were performed on sera. Blood and mosquito samples were tested by Real-Time RT PCR to detect the presence of WNV lineage 1 and 2.Results: The most of the mosquitoes caught belonged to Aedes albopictus, Culex pipiens, Culex hortensis, and Culiseta langiareolata. Two dogs and two horses showed positivity for WNV IgG. The other samples were negative by serological and molecular assays. Conclusion:The results of the animal and entomological surveillance did not show any active WNV circulation during the period object of this study. The IgG seropositivity in a few samples suggested a remote WNV presence. Integration of surveillance and monitoring activities was important to indicate that human case was not autochthonous and the man could have been infected abroad, during the holiday spent in the Caribbean.
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