b . This activation is required for parasite entry into the mammalian cells and is likely to play an important role in modulating the outcome of T. cruzi infection.
Transforming growth factor-β (TGF-β) influences the development of myocardiopathy in Chagas disease through regulation of (i) parasite invasion of heart cells, (ii) an intracellular parasite cycle, (iii) inflammation and immune response, (iv) heart fibrosis and remodeling, and (v) gap junction modulation and heart conduction. In this review, we discuss the rationale for developing TGF-β signaling-interfering therapies as adjuvant approaches for the management of the cardiac alterations of Chagas disease-affected patients.
Surface-associated proteins from Mycobacterium bovis BCG Moreau RDJ are important components of the live Brazilian vaccine against tuberculosis. They are important targets during initial BCG vaccine stimulation and modulation of the host's immune response, especially in the bacterial-host interaction. These proteins might also be involved in cellular communication, chemical response to the environment, pathogenesis processes through mobility, colonization, and adherence to the host cell, therefore performing multiple functions. In this study, the proteomic profile of the surface-associated proteins from M. bovis BCG Moreau was compared to the BCG Pasteur reference strain. The methodology used was 2DE gel electrophoresis combined with mass spectrometry techniques (MALDI-TOF/TOF), leading to the identification of 115 proteins. Of these, 24 proteins showed differential expression between the two BCG strains. Furthermore, 27 proteins previously described as displaying moonlighting function were identified, 8 of these proteins showed variation in abundance comparing BCG Moreau to Pasteur and 2 of them presented two different domain hits. Moonlighting proteins are multifunctional proteins in which two or more biological functions are fulfilled by a single polypeptide chain. Therefore, the identification of such proteins with moonlighting predicted functions can contribute to a better understanding of the molecular mechanisms unleashed by live BCG Moreau RDJ vaccine components.
Dengue fever, caused by the dengue virus (DENV-1, −2, −3, and −4), affects millions of people in the tropical and subtropical regions worldwide. Severe dengue is correlated with high viraemia and cytokine storm, such as high levels of transforming growth factor-β1 (TGF-β1) in the patient's serum. Here, the TGF-β1 signaling was investigated in the context of in vitro viral clearance. Macrophages were infected with DENV-2 at MOI 5 and treated with the TGF-β receptor 1 and 2 inhibitor, GW788388. TGF-β1 expression, signal transduction and viral load were evaluated 48 h after DENV-2 infection by enzyme-linked immunoassay, immunofluorescence, and RT-qPCR assays.Total TGF-β1 level was reduced in 15% after DENV-2 infection, but the secretion of its biologically active form increased threefold during infection, which was followed by the phosphorylation of Smad2 protein. Phosphorylation of Smad2 was reduced by treatment with GW788388 and it was correlated with reduced cytokine production.Importantly, treatment led to a dose-dependent reduction in viral load, ranging from 6.6 × 10 5 RNA copies/ml in untreated cultures to 2.3 × 10 3 RNA copies/ml in cultures treated with 2 ng/ml of GW788388. The anti-TGF-β1 antibody treatment also induced a significant reduction in viral load to 1.6 × 10 3 RNA copies/ml. On the other hand, the addition of recombinant TGF-β1 in infected cultures promoted an increase in viral load to 7.0 × 10 6 RNA copies/ml. These results support that TGF-β1 plays a significant role in DENV-2 replication into macrophages and suggest that targeting TGF-β1 may represent an alternative therapeutic strategy to be explored in dengue infection.
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