scholarly journals Humanized Mice in Dengue Research: A Comparison with Other Mouse Models

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 39 ◽  
Author(s):  
Carolina Coronel-Ruiz ◽  
Hernando Gutiérrez-Barbosa ◽  
Sandra Medina-Moreno ◽  
Myriam L. Velandia-Romero ◽  
Joel V. Chua ◽  
...  
Keyword(s):  
Mouse Models ◽  
Clinical Signs ◽  
Specific Treatment ◽  
Inflammatory Factors ◽  
Humanized Mouse ◽  
Full Spectrum ◽  
Dengue Disease ◽  
Cell Responses ◽  
Life Threatening

Dengue virus (DENV) is an arbovirus of the Flaviviridae family and is an enveloped virion containing a positive sense single-stranded RNA genome. DENV causes dengue fever (DF) which is characterized by an undifferentiated syndrome accompanied by fever, fatigue, dizziness, muscle aches, and in severe cases, patients can deteriorate and develop life-threatening vascular leakage, bleeding, and multi-organ failure. DF is the most prevalent mosquito-borne disease affecting more than 390 million people per year with a mortality rate close to 1% in the general population but especially high among children. There is no specific treatment and there is only one licensed vaccine with restricted application. Clinical and experimental evidence advocate the role of the humoral and T-cell responses in protection against DF, as well as a role in the disease pathogenesis. A lot of pro-inflammatory factors induced during the infectious process are involved in increased severity in dengue disease. The advances in DF research have been hampered by the lack of an animal model that recreates all the characteristics of this disease. Experiments in nonhuman primates (NHP) had failed to reproduce all clinical signs of DF disease and during the past decade, humanized mouse models have demonstrated several benefits in the study of viral diseases affecting humans. In DENV studies, some of these models recapitulate specific signs of disease that are useful to test drugs or vaccine candidates. However, there is still a need for a more complete model mimicking the full spectrum of DENV. This review focuses on describing the advances in this area of research.

scholarly journals SIR Model for Dengue Disease with Effect of Dengue Vaccination

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Pratchaya Chanprasopchai ◽  
I. Ming Tang ◽  
Puntani Pongsumpun
Keyword(s):  
Mathematical Model ◽  
Mortality Rate ◽  
Dengue Virus ◽  
Numerical Solutions ◽  
Specific Treatment ◽  
Sir Model ◽  
Dengue Vaccine ◽  
Dengue Disease ◽  
Modelling Methods

The dengue disease is caused by dengue virus, and there is no specific treatment. The medical care by experienced physicians and nurses will save life and will lower the mortality rate. A dengue vaccine to control the disease is available in Thailand since late 2016. A mathematical model would be an important way to analyze the effects of the vaccination on the transmission of the disease. We have formulated an SIR (susceptible-infected-recovered) model of the transmission of the disease which includes the effect of vaccination and used standard dynamical modelling methods to analyze the effects. The equilibrium states and their stabilities are investigated. The trajectories of the numerical solutions plotted into the 2D planes and 3D spaces are presented. The main contribution is determining the role of dengue vaccination in the model. From the analysis, we find that there is a significant reduction in the total hospitalization time needed to treat the illness.

scholarly journals Generation of Novel Human Red Blood Cell-Bearing Humanized Mouse Models Based on C3-Deficient NOG Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Takuya Yamaguchi ◽  
Ikumi Katano ◽  
Iyo Otsuka ◽  
Ryoji Ito ◽  
Misa Mochizuki ◽  
...  
Keyword(s):  
Mouse Models ◽  
Complement C3 ◽  
Humanized Mouse ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Human Red Blood Cells ◽  
Mouse Macrophages ◽  
C3 Gene ◽  
Humanized Mouse Models

Despite recent advances in immunodeficient mouse models bearing human red blood cells (hRBCs), the elimination of circulating hRBCs by residual innate immune systems remains a significant challenge. In this study, we evaluated the role of mouse complement C3 in the elimination of circulating hRBCs by developing a novel NOG substrain harboring a truncated version of the murine C3 gene (NOG-C3ΔMG2-3). Genetic C3 deletion prolonged the survival of transfused hRBCs in the circulation. Chemical depletion and functional impairment of mouse macrophages, using clodronate liposomes (Clo-lip) or gadolinium chloride (GdCl3), respectively, further extended the survival of hRBCs in NOG-C3ΔMG2-3 mice. Low GdCl3 toxicity allowed the establishment of hRBC-bearing mice, in which hRBCs survived for more than 4 weeks with transfusion once a week. In addition, erythropoiesis of human hematopoietic stem cells (hHSCs) was possible in NOG-C3ΔMG2-3/human GM-CSF-IL-3 transgenic mice with Clo-lip treatment. These findings indicate that mouse models harboring hRBCs can be achieved using NOG-C3ΔMG2-3 mice, which could facilitate studies of human diseases associated with RBCs.

scholarly journals Role of Nbs1 in the activation of the Atm kinase revealed in humanized mouse models

2005 ◽  
Vol 7 (7) ◽  
pp. 675-685 ◽  
Author(s):  
Simone Difilippantonio ◽  
Arkady Celeste ◽  
Oscar Fernandez-Capetillo ◽  
Hua-Tang Chen ◽  
Bernardo Reina San Martin ◽  
...  
Keyword(s):  
Mouse Models ◽  
Humanized Mouse ◽  
Atm Kinase ◽  
Humanized Mouse Models

scholarly journals Targeting Neutrophils in Sepsis: From Mechanism to Translation

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaofei Shen ◽  
Ke Cao ◽  
Yang Zhao ◽  
Junfeng Du
Keyword(s):  
Therapeutic Strategy ◽  
Secondary Infection ◽  
Specific Treatment ◽  
Neutrophil Function ◽  
The Past ◽  
Extracellular Traps ◽  
Promising Strategy ◽  
Threatening Condition ◽  
Life Threatening

Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Although our understanding in the pathophysiological features of sepsis has increased significantly during the past decades, there is still lack of specific treatment for sepsis. Neutrophils are important regulators against invading pathogens, and their role during sepsis has been studied extensively. It has been suggested that the migration, the antimicrobial activity, and the function of neutrophil extracellular traps (NETs) have all been impaired during sepsis, which results in an inappropriate response to primary infection and potentially increase the susceptibility to secondary infection. On the other hand, accumulating evidence has shown that the reversal or restoration of neutrophil function can promote bacterial clearance and improve sepsis outcome, supporting the idea that targeting neutrophils may be a promising strategy for sepsis treatment. In this review, we will give an overview of the role of neutrophils during sepsis and discuss the potential therapeutic strategy targeting neutrophils.

scholarly journals Role of Host and Parasite MIF Cytokines during Leishmania Infection

2020 ◽  
Vol 5 (1) ◽  
pp. 46
Author(s):  
Thomas Holowka ◽  
Richard Bucala
Keyword(s):  
Mouse Models ◽  
Leishmania Major ◽  
Inflammatory Factors ◽  
Leishmania Infection ◽  
Survival Factor ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Human Infections ◽  
Precise Role

Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine that has been extensively characterized in human disease and in mouse models. Its pro-inflammatory functions in mammals includes the retention of tissue macrophages and a unique ability to counteract the immunosuppressive activity of glucocorticoids. MIF also acts as a survival factor by preventing activation-induced apoptosis and by promoting sustained expression of inflammatory factors such as TNF-α and nitric oxide. The pro-inflammatory activity of MIF has been shown to be protective against Leishmania major infection in mouse models of cutaneous disease, however the precise role of this cytokine in human infections is less clear. Moreover, various species of Leishmania produce their own MIF orthologs, and there is evidence that these may drive an inflammatory environment that is detrimental to the host response. Herein the immune response to Leishmania in mouse models and humans will be reviewed, and the properties and activities of mammalian and Leishmania MIF will be integrated into the current understandings in this field. Furthermore, the prospect of targeting Leishmania MIF for therapeutic purposes will be discussed.

scholarly journals Translating Treg Therapy for Inflammatory Bowel Disease in Humanized Mice

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1847
Author(s):  
Sushmita Negi ◽  
Sheetal Saini ◽  
Nikunj Tandel ◽  
Kiran Sahu ◽  
Ravi P.N. Mishra ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Response ◽  
T Cells ◽  
Mouse Models ◽  
Bowel Disease ◽  
Humanized Mice ◽  
Humanized Mouse ◽  
Inflammatory Bowel ◽  
Humanized Mouse Models

Crohn’s disease and ulcerative colitis, two major forms of inflammatory bowel disease (IBD) in humans, afflicted in genetically predisposed individuals due to dysregulated immune response directed against constituents of gut flora. The defective immune responses mounted against the regulatory mechanisms amplify and maintain the IBD-induced mucosal inflammation. Therefore, restoring the balance between inflammatory and anti-inflammatory immunepathways in the gut may contribute to halting the IBD-associated tissue-damaging immune response. Phenotypic and functional characterization of various immune-suppressive T cells (regulatory T cells; Tregs) over the last decade has been used to optimize the procedures for in vitro expansion of these cells for developing therapeutic interventional strategies. In this paper, we review the mechanisms of action and functional importance of Tregs during the pathogenesis of IBD and modulating the disease induced inflammation as well as role of mouse models including humanized mice repopulated with the human immune system (HIS) to study the IBD. “Humanized” mouse models provide new tools to analyze human Treg ontogeny, immunobiology, and therapy and the role of Tregs in developing interventional strategies against IBD. Overall, humanized mouse models replicate the human conditions and prove a viable tool to study molecular functions of human Tregs to harness their therapeutic potential.

Clinical presentation, epidemiological findings, diagnosis, immunity, prevention and control of postweaning multisystemic wasting syndrome (PMWS)

2003 ◽  
Vol 2003 ◽  
pp. 223-223
Author(s):  
J. Segalés ◽  
M. Domingo
Keyword(s):  
Clinical Signs ◽  
Porcine Circovirus Type ◽  
Postweaning Multisystemic Wasting Syndrome ◽  
Porcine Circovirus ◽  
Full Spectrum ◽  
Wasting Syndrome ◽  
And Control ◽  
Porcine Respiratory

Postweaning multisystemic wasting syndrome (PMWS) was initially described in 1991 in Saskatchewan (Canada) and has now been described in all continents rearing pigs but Oceania. Porcine circovirus type 2 (PCV2) is the aetiology of this disease, which has also been called porcine circovirosis in some countries. Although the full spectrum of clinical signs and lesions observed in natural cases of PMWS is very difficult to reproduce under experimental infections using PCV2 alone, little doubt exists on the causal relationship between the virus and the wasting syndrome. Furthermore, the clinical and pathological scope of PCV2 infection has been expanded since 1991, and it has been implicated in other conditions: reproductive disorders, porcine dermatitis and nephropathy syndrome (PDNS), the so-called porcine respiratory disease complex (PRDC), proliferative and necrotising pneumonia (PNP), and congenital tremors. The role of PCV2 in these conditions has not been fully clarified and, in some of these cases, it remains as a controversial issue. The objective of this presentation is to review some practical aspects of PMWS.

scholarly journals Novel humanized-PBMC mouse model with delayed onset of GVHD for preclinical HIV research

2021 ◽  
Author(s):  
Leo Holguin ◽  
Liliana Echavarria ◽  
John C. Burnetta
Keyword(s):  
Mouse Model ◽  
Mouse Models ◽  
Graft Versus Host Disease ◽  
Clinical Signs ◽  
Humanized Mouse ◽  
Graft Versus Host ◽  
Delayed Onset ◽  
Hiv Research ◽  
Humanized Mouse Models ◽  
Hiv 1

Humanized mouse models are based on the engraftment of human cells in immunodeficient mouse strains, most notably the NSG strain. Most used models have a major limitation in common, the development of graft-versus-host disease (GVHD). GVHD not only introduces variabilities into the research data but also leads to animal welfare concerns. A new mouse strain, B6.129S-Rag2 tm1Fwa CD47 tm1Fpl Il2rg tm1Wjl /J which lacks Rag1, IL2rg, and CD47 (triple knockout or TKO), is resistant to GVHD development. We transplanted TKO mice with human peripheral blood mononuclear cells (PBMCs) to establish a new humanized PBMC (hu-PBMC) mouse model. A cohort of these mice was infected with HIV-1 and monitored for plasma HIV viremia and CD4 + T cell depletion. The onset and progression of GVHD were monitored by clinical signs. This study demonstrates that TKO mice transplanted with human PBMCs support engraftment of human immune cells in primary and secondary lymphoid tissues, rectum, and brain. Moreover, the TKO hu-PBMC model supports HIV-1 infection via intraperitoneal, rectal, or vaginal routes, as confirmed by robust plasma HIV viremia and CD4 + T cell depletion. Lastly, TKO mice showed a delayed onset of GVHD clinical signs (∼28 days) and exhibited significant decreases in plasma levels of TNFβ. Based on these results, the TKO hu-PBMC mouse model not only supports humanization and HIV-1 infection but also has a delayed onset of GVHD development, making this model a valuable tool in HIV research. Importance Currently, there is no cure or vaccine for HIV infection, thus continued research is needed to end the HIV pandemic. While many animal models are used in HIV research, none is used more than the humanized mouse model. A major limitation with current humanized mouse models is the development of graft-versus-host disease (GVHD). Here, we show a novel humanized-PBMC mouse model that has a delayed onset GVHD development and supports and models HIV infection comparable to well-established humanized mouse models.

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