Lactate Dehydrogenase-Elevating Virus Infection Inhibits MOG Peptide Presentation by CD11b+CD11c+ Dendritic Cells in a Mouse Model of Multiple Sclerosis.

Infections may affect the course of autoimmune inflammatory diseases of the central nervous system (CNS), such as multiple sclerosis (MS). Infections with lactate dehydrogenase-elevating virus (LDV) protected mice from developing experimental autoimmune encephalomyelitis (EAE), a mouse counterpart of MS. Uninfected C57BL/6 mice immunized with the myelin oligodendrocyte glycoprotein peptide (MOG35-55) experienced paralysis and lost weight at a greater rate than mice who had previously been infected with LDV.

Molecular Research on Plasmodium Infection and Immunity.

The WHO's global strategy for malaria targets a reduction of at least 90% of both incidence and mortality rates for 2030 [...

Cytokine Kinetics during Progression of COVID-19 in Rwanda Patients: Could IL-9/IFNγ Ratio Predict Disease Severity?

For effective treatments and preventive measures against severe COVID-19, it is essential to determine early markers of disease severity in different populations. We analysed the cytokine kinetics of 129 COVID-19 patients with mild symptoms, 68 severe cases, and 20 healthy controls for the first time in Rwanda. Pro-inflammatory (IFNγ, IL-6, TNFα), Treg (IL-10, TGFβ1, TGFβ3), Th9 (IL-9), Th17 (IL-17), and Th2 (IL-4, IL-13) cytokines, total IgM and IgG, as well as gene expressions of , and were measured at day 1, day 7, day 14, day 21, and day 28 post-infection.

Enhanced Mouse Susceptibility to Endotoxin Shock after Infection Is Correlated with Increased Serum Levels of Lipopolysaccharide Soluble Receptors.

Sepsis is a common disease in sub-Saharan Africa and Asia, where malaria is also prevalent. To determine whether infection might enhance susceptibility to endotoxin shock, we used a mouse model of lipopolysaccharide (LPS) administration. Our results indicated that infection in mice strongly enhanced the susceptibility of the host to develop endotoxin shock.

Inhibition of IL-12 heterodimers impairs TLR9-mediated prevention of early mouse plasmacytoma cell growth.

Introduction: Natural prevention of cancer development depends on an efficient immunosurveillance that may be modulated by environmental factors, including infections. Innate lymphoid cytotoxic cells have been shown to play a major role in this immunosurveillance. Interleukin-12 (IL-12) has been suggested to be a key factor in the activation of innate cytotoxic cells after infection, leading to the enhancement of cancer immunosurveillance.

Integrated Analysis of Cytokine Profiles in Malaria Patients Discloses Selective Upregulation of TGF-β1, β3, and IL-9 in Mild Clinical Presentation.

The proper control of Plasmodium infection requires a finely balanced immune response. Here, we evaluated the implication of TGF-β1 and TGF-β3 in this process using novel monoclonal antibodies to measure their plasma concentrations in comparison with other cytokines and the expression of FOXP3 mRNA. Plasma cytokine levels were measured in 80 patients with severe anaemic malaria and 186 with a mild presentation using ELISA, and rtPCR was used to measure FOXP3 mRNA expression.

Possible Interactions between Malaria, Helminthiases and the Gut Microbiota: A Short Review.

Malaria, caused by the species, is an infectious disease responsible for more than 600 thousand deaths and more than 200 million morbidity cases annually. With above 90% of those deaths and cases, sub-Saharan Africa is affected disproportionately. Malaria clinical manifestations range from asymptomatic to simple, mild, and severe disease.

Involvement of Virus-Induced Interferon Production in IgG Autoantibody-Mediated Anemia.

Infection with viruses, such as the lactate dehydrogenase-elevating virus (LDV), is known to trigger the onset of autoimmune anemia through the enhancement of the phagocytosis of autoantibody-opsonized erythrocytes by activated macrophages. Type I interferon receptor-deficient mice show enhanced anemia, which suggests a protective effect of these cytokines, partly through the control of type II interferon production. The development of anemia requires the expression of Fcγ receptors (FcγR) I, III, and IV.

Novel antibodies that selectively block mouse IL-12 enable the re-evaluation of the role of IL-12 in immune protection and pathology.

The dimeric cytokine IL-12 is important in the control of various infections but also contributes to the pathology of certain diseases making it a potential target for therapy. However, its specific inhibition with antibodies is complicated by the fact that its two subunits are present in other cytokines: p40 in IL-23 and p35 in IL-35. This has led to erroneous conclusions like the alleged implication of IL-12 in experimental autoimmune encephalomyelitis (EAE).

Lactate dehydrogenase-elevating virus enhances natural killer cell-mediated immunosurveillance of mouse mesothelioma development.

Background: Viral infections can reduce early cancer development through enhancement of cancer immunosurveillance. This study was performed to analyse this effect of viral infection in a mouse model of solid tumor.

Methods: The experimental model used was the effect of BALB/c mouse infection by lactate dehydrogenase-elevating virus on AB1 mesothelioma cancer development.

The TLR7 ligand R848 prevents mouse graft--host disease and cooperates with anti-interleukin-27 antibody for maximal protection and regulatory T-cell upregulation.

In spite of considerable therapeutic progress, acute graft--host disease still limits allogeneic hematopoietic cell transplantation. We recently reported that mouse infection with nidovirus lactate dehydrogenase elevating virus impairs disease in non-conditioned B6D2F1 recipients of parental B6 spleen cells. As this virus activates TLR7, we tested a pharmacological TLR7 ligand, R848, in this model and observed complete survival if donor and recipients were treated before transplantation.

Effects of interleukin 17A (IL-17A) neutralization on murine hepatitis virus (MHV-A59) infection.

Mice infected with mouse hepatitis virus A59 (MHV-A59) develop hepatitis and autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH), a fact closely related to the release of alarmins such as uric acid and/or high-mobility group box protein 1 (HMGB1). We studied the effect of neutralizing monoclonal antibodies (MAb) against IL-17A in our model of mouse MHV-A59-infection. MAb anti-IL-17F and anti-IFNγ were used to complement the study.

Mouse nidovirus LDV infection alleviates graft versus host disease and induces type I IFN-dependent inhibition of dendritic cells and allo-responsive T cells.

Introduction: Viruses have developed multiple mechanisms to alter immune reactions. In 1969, it was reported that lactate dehydrogenase-elevating virus (LDV), a single stranded positive sense mouse nidovirus, delays skin allograft rejection and inhibits spleen alterations in graft versus host disease (GVHD). As the underlying mechanisms have remained unresolved and given the need for new therapies of this disease, we reassessed the effects of the virus on GVHD and tried to uncover its mode of action.

Novel highly specific anti-periostin antibodies uncover the functional importance of the fascilin 1-1 domain and highlight preferential expression of periostin in aggressive breast cancer.

Periostin (POSTN), a secreted homodimeric protein that binds integrins αvβ3, αvβ5, and α6β4, was originally found to be expressed in fetal tissues and in the adult upon injury particularly bone fractures due to its role in remodelling and repair. Recently it was found to be over-expressed in human breast cancer and a variety of other tumour types including head and neck squamous cell carcinoma, where its overexpression correlates with increased tumour invasion. Progress in studying its functional role in tumour pathogenesis has been hampered by the paucity of antibodies for its specific and sensitive detection.

Involvement of Fcα/μ Receptor in IgM Anti-Platelet, but Not Anti-Red Blood Cell Autoantibody Pathogenicity in Mice.

IgM anti-mouse platelet autoantibodies cause thrombocytopenia by mediating uptake of opsonized thrombocytes, whereas IgM anti-erythrocyte autoantibodies induce anemia through a phagocytosis-independent cell destruction. In this article, we show that infection with lactate dehydrogenase-elevating virus, a benign mouse arterivirus, exacerbates the pathogenicity of IgM anti-platelet, but not anti-erythrocyte autoantibodies. To define the role of Fcα/μ receptor (Fcα/μR) in IgM-mediated thrombocytopenia and anemia, we generated mice deficient for this receptor.

Modulation of the host microenvironment by a common non-oncolytic mouse virus leads to inhibition of plasmacytoma development through NK cell activation.

Although many cells undergo transformation, few actually develop into tumours, due to successful mechanisms of immunosurveillance. To investigate whether an infectious agent may play a role in this process, the growth of a plasmacytoma was investigated in mice infected by lactate dehydrogenase-elevating virus. Acutely infected animals were significantly protected against tumour development.

Lactate dehydrogenase-elevating virus infection: an experimental model of immune microenvironment modulation.

Lactate dehydrogenase-elevating virus (LDV), a mouse arterivirus, is characterized by a lifelong viremia, despite antiviral innate and adaptative immune response. It induces strong modifications of the host immune microenvironment, including macrophage and natural killer cell activation, secretion of pro-inflammatory cytokines, modulation of T helper cell differentiation and polyclonal activation of B-lymphocytes. This modification of the immune microenvironment results in the protection against some diseases such as allergies, graft-versus-host reaction, experimental autoimmune encephalitis, and growth of some tumors.

Changes in antibody specificities and cytokine release after infection with lactate dehydrogenase-elevating virus.

Lactate dehydrogenase-elevating virus (LDV) is an apparently innocuous and persistent virus that can modify mouse immune reactions. We have shown that LDV-infected mice immunized with human growth hormone (hGH) showed a deep modification of the specificity of the anti-hGH antibodies (Ab) in CBA/Ht mice but not BALB/c animals. The aim of this work was to extend the previous observations to another mouse strain, C57BL/6, as well as to an antigen unrelated to hGH, ovalbumin (OVA), and to explore at the same time the production of various cytokines at serum and cellular levels.

Antibody-independent thrombocytopenia in lactate dehydrogenase-elevating virus-infected mice.

Previously we demonstrated that antibody-mediated thrombocytopenia is strongly enhanced by lactate dehydrogenase-elevating virus (LDV) infection. Here we report that mice infected with LDV develop a moderate thrombocytopenia, even in the absence of immunoglobulins or Fc receptors. A similar decrease of platelet counts was observed after mouse hepatitis virus infection.

Modulation of lipopolysaccharide receptor expression by lactate dehydrogenase-elevating virus.

Lactate dehydrogenase-elevating virus (LDV) exacerbates mouse susceptibility to endotoxin shock through enhanced tumour necrosis factor (TNF) production by macrophages exposed to lipopolysaccharide (LPS). However, the in vivo enhancement of TNF production in response to LPS induced by the virus largely exceeds that found in vitro with cells derived from infected animals. Infection was followed by a moderate increase of Toll-like receptor (TLR)-4/MD2, but not of membrane CD14 expression on peritoneal macrophages.

Characterization of the T-lymphocyte response elicited by mouse immunization with rat platelets.

Objective: Immunization of normal CBA mice with rat platelets leads to an autoantibody response directed against mouse platelets. The purpose of this work was to determine the involvement of T lymphocytes in this response.

Materials And Methods: T-lymphocyte responses were analyzed in vivo by depletion and transfer experiments and ex vivo by proliferation assay and cytokine measurements.

Immunoglobulin M antiplatelet autoantibodies from mice immunized with rat platelets induce thrombocytopenia and platelet function impairment.

Antiplatelet monoclonal autoantibodies (mAbs) were derived from CBA mice immunized with rat platelets. Two IgM antiplatelet mAbs were further analyzed. L1C43 mAb bound a 150-160 kDa antigen, recognized activated platelets better than resting ones and impaired platelet adhesion, but not clot retraction.

Production of protective gamma interferon by natural killer cells during early mouse hepatitis virus infection.

Gamma interferon (IFN-gamma) plays a major role in the protection against lethal infection with mouse hepatitis virus A59. IFN-gamma production reaches a maximum level 2 days after viral inoculation, especially in liver immune cells. Among these cells, natural killer cells are the major producers of this cytokine.

CD66a (CEACAM1) expression by mouse natural killer cells.

CD66a (CEACAM1), an adhesion molecule that has regulatory function on T lymphocytes, was found to be expressed on a minority of mouse natural killer (NK) cells, especially in the liver. CD66a expression on NK cells depended on their differentiation stage, with highest levels on immature CD49b(-)NK cells. Expression of CD66a on NK cells was strongly enhanced by in vitro activation with interleukin-12 (IL-12) and IL-18.

Distinct gamma interferon-production pathways in mice infected with lactate dehydrogenase-elevating virus.

Two distinct pathways of gamma interferon (IFN-gamma) production have been found in mice infected with lactate dehydrogenase-elevating virus. Both pathways involve natural killer cells. The first is mostly interleukin-12-independent and is not controlled by type I interferons.