Search results for "Gamma"

Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ.

2013

Due to a unique pattern of CD8 T-cell response induced by cytomegaloviruses (CMVs), live attenuated CMVs are attractive candidates for vaccine vectors for a number of clinically relevant infections and tumors. NKG2D is one of the most important activating NK cell receptors that plays a role in costimulation of CD8 T cells. Here we demonstrate that the expression of CD8 T-cell epitope of Listeria monocytogenes by a recombinant mouse CMV (MCMV) expressing the NKG2D ligand retinoic acid early-inducible protein 1-gamma (RAE-1γ) dramatically enhanced the effectiveness and longevity of epitope-specific CD8 T-cell response and conferred protection against a subsequent challenge infection with List…

IFN? expression inhibits LHBs storage disease and ground glass hepatocyte appearance, but exacerbates inflammation and apoptosis in HBV surface prote…

2006

BACKGROUND/AIMS Interferon gamma (IFNgamma) controls hepatitis B virus replication. As systemic application may cause severe adverse effects, approaches of liver-directed IFNgamma gene therapy may represent an attractive alternative for treatment of chronic viral hepatitis B and thus needs testing in vivo in suitable animal models. METHODS We therefore crossbred Alb-1HBV transgenic mice overexpressing the large HBV surface protein (LHBs) in their livers and developing LHBs storage disease and ground glass hepatocyte appearance with SAP-IFNgamma transgenic animals previously shown to exhibit constitutive hepatic IFNgamma expression, and analyzed the resulting double-transgenic offspring. RES…

Chronic inflammatory cardiomyopathy of interferon γ-overexpressing transgenic mice is mediated by tumor necrosis factor-α.

2011

We recently described a model of inflammatory cardiomyopathy in interferon (IFN)-γ overexpressing transgenic mice stably circulating IFN-γ in the serum referred to as SAP–-IFN-γ mice. SAP–IFN-γ transgenic mice show cardiac infiltration by mononuclear leukocytes, culminating in dilated cardiomyopathy characterized by an increase of left ventricular end diastolic diameter and reduction of fractional shortening. We hypothesized that the pathological mechanism underlying SAP–IFN-γ cardiomyopathy might be mediated by (auto)immune processes or tumor necrosis factor (TNF)-α synthesis from IFN-γ–activated macrophages. To verify these hypotheses, we crossed SAP–IFN-γ transgenic mice with immunodefic…

A key pathogenic role for the STAT1/T-bet signaling pathway in T-cell-mediated liver inflammation.

2003

TH1 cytokines have been suggested to contribute to the pathogenesis of T-cell-mediated liver injury and inflammation. However, the molecular signaling pathways involved in such injury are still poorly understood. In the present study, we investigated the role of the STAT1/T-bet signaling pathway in a murine model of T-cell-mediated liver inflammation induced by the application of concanavalin A (Con A) using newly created STAT1 transgenic mice as well as STAT1- and T-bet-deficient mice. Liver injury induced by Con A was associated with an increase of both pSTAT1 and T-bet levels in the liver. Furthermore, functional studies suggested a pathogenic role for STAT1 in Con A-induced liver injury…

Severe hepatic injury in interleukin 18 (IL-18) transgenic mice: a key role for IL-18 in regulating hepatocyte apoptosis in vivo.

2004

Background: Interleukin 18 (IL-18) is a cytokine with pleiotropic activity that augments T helper 1 responses and cytotoxic activity of natural killer cells. Methods: To assess the function of IL-18 in vivo, we generated IL-18 transgenic (IL-18 Tg) mice under the control of a CD2 promoter/enhancer construct. Results: Macroscopically, IL-18 Tg mice showed reduced relative liver weight compared with wild-type littermates. TUNEL assays demonstrated increased hepatocyte apoptosis, and primary hepatocytes isolated from IL-18 Tg mice exhibited an increased spontaneous apoptosis rate. Furthermore, cross linking of Fas increased significantly the apoptosis rate in hepatocytes isolated from wild- ty…

Fatal neuroinvasion and SARS-CoV-2 tropism in K18-hACE2 mice is partially independent on hACE2 expression

2022

ABSTRACTAnimal models recapitulating distinctive features of severe COVID-19 are critical to enhance our understanding of SARS-CoV-2 pathogenesis. Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model of SARS-CoV-2 infection. The precise mechanisms of lethality in this mouse model remain unclear. Here, we evaluated the spatiotemporal dynamics of SARS-CoV-2 infection for up to 14 days post-infection. Despite infection and moderate pneumonia, rapid clinical decline or death of mice was invariably associated with viral neuroinvasion and direct neuronal injury (including brain and spinal neurons). Neuroinv…

Immune characterization of the HBHA-specific response in Mycobacterium tuberculosis-infected patients with or without HIV infection.

2017

Introduction RD1-based Interferon-γ Release Assays (IGRAs) cannot distinguish latent from active tuberculosis (TB) disease. Conversely, a positive response to heparin-binding haemagglutinin (HBHA)-based IGRAs, among TB-infected subjects, correlates with Mycobacterium tuberculosis (Mtb) containment and low risk of TB progression. The aim of this study was to characterize HBHA-immune responses in HIV-infected and uninfected subjects with active TB or latent TB infection (LTBI). Methods 49 subjects were prospectively enrolled: 22 HIV-uninfected (13 TB, 9 LTBI) and 27 HIV-infected (12 HIV-TB, 15 HIV-LTBI). Whole blood and peripheral blood mononuclear cells were stimulated with HBHA and RD1 anti…

Larval morphology, genetic divergence, and contrasting levels of host manipulation between forms of Pomphorhynchus laevis (Acanthocephala)

2004

Studies on parasite species with a wide geographic and ecological range may be confounded by still equivocal taxonomic identification. Here, we investigated genetic polymorphism and behavioural changes induced in a common intermediate host, in two different forms of Pomphorhynchus laevis based on the morphology of the larval infective stage (cystacanth). A 'smooth type' (S) and a 'wrinkled type' (W) of cystacanth were distinguished based on their surface and shape. We analysed sequence divergence at both nuclear (ribosomal gene 18S rDNA, and ribosomal internal transcribed spacers, ITS1/ITS2) and mitochondrial (cytochrome c oxidase subunit 1) genes of P. laevis cystacanths and adults at vari…

Molecular markers for systematic identification and population genetics of the invasive Ponto-Caspian freshwater gammarid Dikerogammarus villosus (Cr…

2006

The Ponto-Caspian amphipod, Dikerogammarus villosus, is an invasive species of many European rivers. First, we show that size difference of nrDNA ITS1 allows discriminating D. villosus from Dikerogammarus bispinosus, a closely related but morphologically hardly distinguishable species. Second, we present two types of polymorphic markers for D. villosus, three microsatellites and two single nucleotide polymorphisms (SNPs) of mtDNA COI gene, which were scored by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). These markers will be very useful in studying population genetics of D. villosus.

2006

On the basis of their biological function, potential genetic candidates for susceptibility to rheumatoid arthritis can be postulated. IFNGR1, encoding the ligand-binding chain of the receptor for interferon gamma, IFNγR1, is one such gene because interferon gamma is involved in the pathogenesis of the disease. In the coding sequence of IFNGR1, two nucleotide positions have been described to be polymorphic in the Japanese population. We therefore investigated the association of those two IFNGR1 single nucleotide polymorphisms with rheumatoid arthritis in a case-control study in a central European population. Surprisingly, however, neither position was polymorphic in the 364 individuals exami…