Raman spectroscopy on live mouse early embryo while it continues to develop into blastocyst in vitro

et al. 2021

Front. Immunol.

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Typically occurring during secondary dengue virus (DENV) infections, dengue hemorrhagic fever (DHF) causes abnormal immune responses, as well as endothelial vascular dysfunction, for which the responsible viral factor remains unclear. During peak viremia, the plasma levels of virion-associated envelope protein domain III (EIII) increases to a point at which cell death is sufficiently induced in megakaryocytes in vitro. Thus, EIII may constitute a virulence factor for endothelial damage. In this study, we examined endothelial cell death induced by treatment with DENV and EIII in vitro. Notably, pyroptosis, the major type of endothelial cell death observed, was attenuated through treatment with Nlrp3 inflammasome inhibitors. EIII injection effectively induced endothelial abnormalities, and sequential injection of EIII and DENV-NS1 autoantibodies induced further vascular damage, liver dysfunction, thrombocytopenia, and hemorrhage, which are typical manifestations in DHF. Under the same treatments, pathophysiological changes in the Nlrp3 inflammasome–deficient mice were notably reduced compared with those in the wild-type mice. These results suggest that the Nlrp3 inflammasome constitutes a potential therapeutic target for treating DENV-induced hemorrhage in DHF.

Section: Methodsmentioning

confidence: 99%

Exposure to Dengue Envelope Protein Domain III Induces Nlrp3 Inflammasome-Dependent Endothelial Dysfunction and Hemorrhage in Mice

Lien

et al. 2021

Front. Immunol.

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“…Experimental animals were maintained at a specific pathogen free condition with consistent temperature and humidity controls, and 12 h light/dark cycle 27,29,32,33 . Acute liver damage and thrombocytopenia were chemically induced using TAA in rat and mouse models by employing a method modified from those previously reported 34,35 .…”

Section: Methodsmentioning

confidence: 99%

Thioacetamide-induced liver damage and thrombocytopenia is associated with induction of antiplatelet autoantibody in mice

Lin

et al. 2019

Sci Rep

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Thrombocytopenia is usually associated with liver injury, elevated plasma aspartate aminotransferase and alanine aminotransferase levels, and high antiplatelet immunoglobulin (Ig) titers, although the mechanism behind these effects remains elusive. Deciphering the mechanism behind acute liver disease–associated thrombocytopenia may help solve difficulties in routine patient care, such as liver biopsy, antiviral therapy, and surgery. To determine whether liver damage is sufficient per se to elicit thrombocytopenia, thioacetamide (TAA)-induced hepatitis rodent models were employed. The analysis results indicated that TAA treatment transiently induced an elevation of antiplatelet antibody titer in both rats and mice. B-cell-deficient (BCD) mice, which have loss of antibody expression, exhibited markedly less thrombocytopenia and liver damage than wild-type controls. Because TAA still induces liver damage in BCD mice, this suggests that antiplatelet Ig is one of the pathogenic factors, which play exacerbating role in the acute phase of TAA-induced hepatitis. TNF-α was differentially regulated in wild-type versus BCD mice during TAA treatment, and anti-TNF treatment drastically ameliorated antiplatelet Ig induction, thrombocytopenia, and liver injury, suggesting that the TNF pathway plays a critical role in the disease progression.

“…Using SDS-PAGE and NIH-Image J software (version 1.6.2), the purified Igs were estimated approximately 87%-91% pure. Experimental mice and rabbits were maintained at a specific pathogen free condition with consistent temperature and humidity controls, and 12 h light/dark cycles [75][76][77] . All protocols used in rabbit and mouse experiments were carried out in accordance with the guidelines of and approved by the Institutional Animal Care and Use Committee of Tzu-Chi University (approval ID: 101019).…”

Section: Methodsmentioning

confidence: 99%

Suppressed humoral immunity is associated with dengue nonstructural protein NS1-elicited anti-death receptor antibody fractions in mice

Tsai

et al. 2020

Sci Rep

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Dengue virus (DENV) infections may cause life-threatening dengue hemorrhagic fever (DHF).Suppressed protective immunity was shown in these patients. Although several hypotheses have been formulated, the mechanism of DENV-induced immunosuppression remains unclear. Previously, we found that cross-reactive antibodies against tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 1 (death receptor 4 [DR4]) were elicited in DHF patients, and that anti-DR4 autoantibody fractions were elicited by nonstructural protein 1 (NS1) immunizations in experimental mice. In this study, we found that anti-DR4 antibodies could suppress B lymphocyte function in vitro and in vivo. Treatment with the anti-DR4 immunoglobulin (Ig) induced caspase-dependent cell death in immortalized B lymphocyte Raji cells in vitro. Anti-DR4 Igs elicited by NS1 and DR4 immunizations markedly suppressed mouse spleen transitional T2 B (IgM + IgD + ), bone marrow pre-pro-B (B220 + CD43 + ), pre-B (B220 + CD43 − ), and mature B cell (B220 + IgD + ) subsets in mice. Furthermore, functional analysis revealed that the pre-elicitation of anti-NS1 and anti-DR4 Ig titers suppressed subsequently neutralizing antibody production by immunization with DENV envelop protein. Our data suggest that the elicitation of anti-DR4 titers through DENV NS1 immunization plays a suppressive role in humoral immunity in mice.The dengue virus (DENV) is a mosquito-borne single positive-stranded RNA virus belonging to the Flaviviridae family (genus Flavivirus); the 4 major serotypes of DENV cause self-limiting dengue fever (DF) and life-threatening dengue hemorrhagic fever (DHF) 1 . It has been estimated that 50 million cases of DENV infections occur, and approximately 500,000 patients have been hospitalized with DHF, mainly in tropical and subtropical regions 2 . Evidence has suggested that because of the geographical extension of DENV infection and increases in the number of DENV cases and disease severity, DF and DHF have become major public health problems, with more than one-third of the global population residing in high-transmission-risk areas 3-5 . DHF is a complex disease, and its mechanism remains elusive. Currently, no specific treatment or effective vaccine is available for immunization cycle) in 1 wk intervals and then the bone marrow and spleen lymphocytes were analyzed 7 d later using aforementioned B cell markers. To analyze the potential suppressive effect of prior immunizations of NS1 on later induction of neutralizing antibody, C57BL/6J mice were first immunized with rGST, rNS1, rDR4 and rTACI by 2 immunization cycles (50 µg immunogen/mouse/immunization cycle) and then immunized with 2 additional immunization cycles of DENV rEIII in 1 wk intervals. The anti-EIII titer and the DENV-neutralizing property of these polyclonal antibody fractions were then analyzed.Statistical analyses. The means, standard deviations, and statistics for the quantifiable data were calculated using Microsoft Office Excel 2003, SigmaPlot 10 and SPSS 17. Significance of data...