scholarly journals Organ-Specific Expression of IL-1 Receptor Results in Severe Liver Injury in Type I Interferon Receptor Deficient Mice

2019 ◽  
Vol 10 ◽  
Author(s):  
Martina Anzaghe ◽  
Theresa Resch ◽  
Elea Schaser ◽  
Stefanie Kronhart ◽  
Clara Diez ◽  
...  
Keyword(s):  
Liver Injury ◽  
Type I Interferon ◽  
Type I ◽  
Severe Liver ◽  
Specific Expression ◽  
Interferon Receptor ◽  
Organ Specific ◽  
Organ Specific Expression ◽  
Deficient Mice

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

2021 ◽  
Vol 22 (16) ◽  
pp. 9027
Author(s):  
Sarah Legrain ◽  
Dan Su ◽  
Mélanie Gaignage ◽  
Cor Breukel ◽  
Jill Claassens ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Type I Interferon ◽  
Type I ◽  
Type Ii ◽  
Interferon Production ◽  
Activated Macrophages ◽  
Wild Type ◽  
Fcγ Receptors ◽  
Interferon Receptor ◽  
Deficient Mice

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. Whereas LDV infection decreases FcγR III expression, it enhances FcγR I and IV expression in wild-type animals. The LDV-associated increase in the expression of FcγR I and IV is largely reduced in type I interferon receptor-deficient mice, through both type II interferon-dependent and -independent mechanisms. Thus, the regulation of the expression of FcγR I and IV, but not III, by interferons may partly explain the exacerbating effect of LDV infection on anemia that results from the enhanced phagocytosis of IgG autoantibody-opsonized erythrocytes.

scholarly journals Exploring Crimean-Congo Hemorrhagic Fever Virus-Induced Hepatic Injury Using Antibody-Mediated Type I Interferon Blockade in Mice

2018 ◽  
Vol 92 (21) ◽  
Author(s):  
Michael E. Lindquist ◽  
Xiankun Zeng ◽  
Louis A. Altamura ◽  
Sharon P. Daye ◽  
Korey L. Delp ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Damage ◽  
Hepatic Injury ◽  
Type I Interferon ◽  
Small Animal ◽  
Hemorrhagic Fever ◽  
Acute Disease ◽  
Type I ◽  
Severe Liver ◽  
Hemorrhagic Fever Virus

ABSTRACT Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe hepatic injury in humans. However, the mechanism(s) causing this damage is poorly characterized. CCHFV produces an acute disease, including liver damage, in mice lacking type I interferon (IFN-I) signaling due to either STAT-1 gene deletion or disruption of the IFN-I receptor 1 gene. Here, we explored CCHFV-induced liver pathogenesis in mice using an antibody to disrupt IFN-I signaling. When IFN-I blockade was induced within 24 h postexposure to CCHFV, mice developed severe disease with greater than 95% mortality by 6 days postexposure. In addition, we observed increased proinflammatory cytokines, chemoattractants, and liver enzymes in these mice. Extensive liver damage was evident by 4 days postexposure and was characterized by hepatocyte necrosis and the loss of CLEC4F-positive Kupffer cells. Similar experiments in CCHFV-exposed NOD-SCID-γ (NSG), Rag2-deficient, and perforin-deficient mice also demonstrated liver injury, suggesting that cytotoxic immune cells are dispensable for hepatic damage. Some apoptotic liver cells contained viral RNA, while other apoptotic liver cells were negative, suggesting that cell death occurred by both intrinsic and extrinsic mechanisms. Protein and transcriptional analysis of livers revealed that activation of tumor necrosis factor superfamily members occurred by day 4 postexposure, implicating these molecules as factors in liver cell death. These data provide insights into CCHFV-induced hepatic injury and demonstrate the utility of antibody-mediated IFN-I blockade in the study of CCHFV pathogenesis in mice. IMPORTANCE CCHFV is an important human pathogen that is both endemic and emerging throughout Asia, Africa, and Europe. A common feature of acute disease is liver injury ranging from mild to fulminant hepatic failure. The processes through which CCHFV induces severe liver injury are unclear, mostly due to the limitations of existing small-animal systems. The only small-animal model in which CCHFV consistently produces severe liver damage is mice lacking IFN-I signaling. In this study, we used antibody-mediated blockade of IFN-I signaling in mice to study CCHFV liver pathogenesis in various transgenic mouse systems. We found that liver injury did not depend on cytotoxic immune cells and observed extensive activation of death receptor signaling pathways in the liver during acute disease. Furthermore, acute CCHFV infection resulted in a nearly complete loss of Kupffer cells. Our model system provides insight into both the molecular and the cellular features of CCHFV hepatic injury.

scholarly journals Mayaro virus replication restriction and induction of muscular inflammation in mice are dependent on age and type-I interferon response

2019 ◽  
Author(s):  
CM Figueiredo ◽  
RL Neris ◽  
DG Leopoldino ◽  
JS Almeida ◽  
JS dos-Santos ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Adult Type ◽  
Innate And Adaptive Immunity ◽  
High Prevalence ◽  
Interferon Receptor ◽  
Mayaro Virus ◽  
Deficient Mice

AbstractMayaro virus (MAYV) is an emergent Arbovirus belonging to the Alphavirus genus from theTogaviridaefamily which has been circulated in forest regions of American continent through small outbreaks. Recent studies warned for the risk of MAYV dispersion to new areas and for the potential establishment of an urban epidemic cycle. Similar to Chikungunya and other arthritogenic Alphavirus, MAYV-induced disease shows a high prevalence of arthralgia and myalgia that can persist for months. Despite this, knowledge regarding pathogenesis, characteristics of host immune response, and resolution of MAYV infections are still limited. Here we investigated the dependence of age, innate and adaptive immunity for the control of MAYV replication and induction of inflammation in mice. We observed that age and type I interferon response are related to restriction of MAYV infection and tissue inflammation in mice. Moreover, we showed that MAYV continues to replicate persistently in adult recombination activation gene-1 efficient mice (RAG1−/−), indicating that adaptive immunity is essential to MAYV clearance. Despite chronic replication, infected adult RAG1−/−mice did not develop an apparent signal of muscle damage at late infection. On the other hand, MAYV infection induces muscular and paw inflammation in young WT and adult Type I Interferon receptor deficient mice (IFNAR−/−). In addition, MAYV infection triggers an increase in the expression of pro-inflammatory mediators, such as TNF, IL-6, KC, IL-1β, MCP-1, and RANTES, in muscle tissue, and decreases TGF-β expression. Taken together, our study contributes to the comprehension of MAYV pathogenesis, and describes a translational mouse model for further studies of MAYV infection, as well for testing vaccine and therapeutic strategies against this virus.Author SummaryMAYV-induced disease presents a high prevalence of arthralgia and myalgia that potentially persist for months, which is characteristic of the arthritogenic Alphavirus group. However, information regarding MAYV infection and the molecular mechanism of pathogenesis is still scarce. Here we investigated the dependence of age, innate and adaptive immunity for the control of MAYV replication and induction of inflammation in mice. We observed that tissue inflammation and the restriction of MAYV replication in mice are affected by aging and type I interferon response. Besides, we also showed that adaptive immunity was important for MAYV clearance in adult mice. Histological analyses demonstrated that MAYV replication triggered muscular and paw inflammation in young WT and adult type-I interferon receptor deficient mice. In addition, the level of expression of several pro-inflammatory cytokines was increased in the muscle MAYV-infected mice. Our data provide an advance for understanding the molecular mechanism involved in MAYV pathogenesis, as well as describes anin vivomodel for further investigations on MAYV infection and for antiviral compounds and vaccine testing.

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