Early Transcriptional Differences in the Brain of Theiler’s Virus-infected Mouse Strains Reveal Delayed Antiviral Immune Responses in SJL/J mice

2020 ◽  
Vol 174 ◽  
pp. 178
Author(s):  
M. Ciurkiewicz ◽  
S. Floess ◽  
M. Beckstette ◽  
M. Kummerfeld ◽  
W. Baumgartner ◽  
...  
Keyword(s):  
Immune Responses ◽  
Infected Mouse ◽  
Mouse Strains ◽  
Theiler's Virus ◽  
The Brain

scholarly journals Evidence for Differential Roles for NKG2D Receptor Signaling in Innate Host Defense against Coronavirus-Induced Neurological and Liver Disease

2007 ◽  
Vol 82 (6) ◽  
pp. 3021-3030 ◽  
Author(s):  
Kevin B. Walsh ◽  
Melissa B. Lodoen ◽  
Robert A. Edwards ◽  
Lewis L. Lanier ◽  
Thomas E. Lane
Keyword(s):  
Liver Disease ◽  
Immune Responses ◽  
Host Defense ◽  
Nk Cell ◽  
Hepatitis Virus ◽  
Innate Immune ◽  
Liver Pathology ◽  
Innate Immune Responses ◽  
Ifn Γ ◽  
The Brain

ABSTRACT Infection of SCID mice with a recombinant murine coronavirus (mouse hepatitis virus [MHV]) expressing the T-cell chemoattractant CXC chemokine ligand 10 (CXCL10) resulted in increased survival and reduced viral burden within the brain and liver compared to those of mice infected with an isogenic control virus (MHV), supporting an important role for CXCL10 in innate immune responses following viral infection. Enhanced protection in MHV-CXCL10-infected mice correlated with increased gamma interferon (IFN-γ) production by infiltrating natural killer (NK) cells within the brain and reduced liver pathology. To explore the underlying mechanisms associated with protection from disease in MHV-CXCL10-infected mice, the functional contributions of the NK cell-activating receptor NKG2D in host defense were examined. The administration of an NKG2D-blocking antibody to MHV-CXCL10-infected mice did not reduce survival, dampen IFN-γ production in the brain, or affect liver pathology. However, NKG2D neutralization increased viral titers within the liver, suggesting a protective role for NKG2D signaling in this organ. These data indicate that (i) CXCL10 enhances innate immune responses, resulting in protection from MHV-induced neurological and liver disease; (ii) elevated NK cell IFN-γ expression in the brain of MHV-CXCL10-infected mice occurs independently of NKG2D; and (iii) NKG2D signaling promotes antiviral activity within the livers of MHV-infected mice that is not dependent on IFN-γ and tumor necrosis factor alpha secretion.

scholarly journals The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced AmyloidβBinding Antibodies on Cynomolgus Monkeys and Guinea Pigs

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Akira Yano ◽  
Kaori Ito ◽  
Yoshikatsu Miwa ◽  
Yoshito Kanazawa ◽  
Akiko Chiba ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tetanus Toxoid ◽  
Guinea Pigs ◽  
Peptide Vaccine ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
Peptide Vaccination ◽  
Binding Profile ◽  
Cynomolgus Monkeys ◽  
The Brain

The reduction of brain amyloid beta (Aβ) peptides by anti-Aβantibodies is one of the possible therapies for Alzheimer’s disease. We previously reported that the Aβpeptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT) induced anti-Aβantibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβantibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ40, and Aβ42compared to Aβfibrils. The levels of serum anti-Aβantibodies and plasma Aβpeptides increased in both animals and decreased the brain Aβ40level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβantibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβpeptides and their toxic effects via clearance of Aβpeptides by generated antibodies.

scholarly journals Influence of systemic immune responses in the brain after wound injury of tail amputation in zebrafish

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Xiang‐Ke Chen ◽  
Alvin Chun‐Hang Ma ◽  
Raymond Chuen‐Chung Chang
Keyword(s):  
Immune Responses ◽  
The Brain

scholarly journals Stability of Lentiviral Vector-Mediated Transgene Expression in the Brain in the Presence of Systemic Antivector Immune Responses

2005 ◽  
Vol 16 (6) ◽  
pp. 741-751 ◽  
Author(s):  
Evelyn Abordo-Adesida ◽  
Antonia Follenzi ◽  
Carlos Barcia ◽  
Sandra Sciascia ◽  
Maria G. Castro ◽  
...  
Keyword(s):  
Immune Responses ◽  
Transgene Expression ◽  
Lentiviral Vector ◽  
The Brain

scholarly journals A Protective Role for Interleukin-1 Signaling during Mouse Adenovirus Type 1-Induced Encephalitis

2016 ◽  
Vol 91 (4) ◽  
Author(s):  
Luiza A. Castro-Jorge ◽  
Carla D. Pretto ◽  
Asa B. Smith ◽  
Oded Foreman ◽  
Kelly E. Carnahan ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Time Course ◽  
Interleukin 1 ◽  
Adenovirus Type ◽  
Mouse Strains ◽  
Complex Nature ◽  
Type I ◽  
Viral Loads ◽  
The Brain

ABSTRACT Interleukin-1β (IL-1β), an inflammatory cytokine and IL-1 receptor ligand, has diverse activities in the brain. We examined whether IL-1 signaling contributes to the encephalitis observed in mouse adenovirus type 1 (MAV-1) infection, using mice lacking the IL-1 receptor (Il1r1 −/− mice). Il1r1 −/− mice demonstrated reduced survival, greater disruption of the blood-brain barrier (BBB), higher brain viral loads, and higher brain inflammatory cytokine and chemokine levels than control C57BL/6J mice. We also examined infections of mice defective in IL-1β production (Pycard −/− mice) and mice defective in trafficking of Toll-like receptors to the endosome (Unc93b1 −/− mice). Pycard −/− and Unc93b1 −/− mice showed lower survival (similar to Il1r1 −/− mice) than control mice but, unlike Il1r1 −/− mice, did not have increased brain viral loads or BBB disruption. Based on the brain cytokine levels, MAV-1-infected Unc93b1 −/− mice had a very different inflammatory profile from infected Il1r1 −/− and Pycard −/− mice. Histological examination demonstrated pathological findings consistent with encephalitis in control and knockout mice; however, intranuclear viral inclusions were seen only in Il1r1 −/− mice. A time course of infection of control and Il1r1 −/− mice evaluating the kinetics of viral replication and cytokine production revealed differences between the mouse strains primarily at 7 to 8 days after infection, when mice began succumbing to MAV-1 infection. In the absence of IL-1 signaling, we noted an increase in the transcription of type I interferon (IFN)-stimulated genes. Together, these results indicate that IL-1 signaling is important during MAV-1 infection and suggest that, in its absence, increased IFN-β signaling may result in increased neuroinflammation. IMPORTANCE The investigation of encephalitis pathogenesis produced by different viruses is needed to characterize virus and host-specific factors that contribute to disease. MAV-1 produces viral encephalitis in its natural host, providing a good model for studying factors involved in encephalitis development. We investigated the role of IL-1 signaling during MAV-1-induced encephalitis. Unexpectedly, the lack of IL-1 signaling increased the mortality and inflammation in mice infected with MAV-1. Also, there was an increase in the transcription of type I IFN-stimulated genes that correlated with the observed increased mortality and inflammation. The findings highlight the complex nature of encephalitis and suggests that IL-1 has a protective effect for the development of MAV-1-induced encephalitis.

scholarly journals Replication Kinetics, Cell Tropism, and Associated Immune Responses in SARS-CoV-2- and H5N1 Virus-Infected Human Induced Pluripotent Stem Cell-Derived Neural Models

mSphere ◽  
2021 ◽  
Author(s):  
Lisa Bauer ◽  
Bas Lendemeijer ◽  
Lonneke Leijten ◽  
Carmen W. E. Embregts ◽  
Barry Rockx ◽  
...  
Keyword(s):  
Immune Responses ◽  
H5n1 Virus ◽  
Induced Pluripotent Stem Cell ◽  
Neurological Complications ◽  
Olfactory Nerve ◽  
Cell Tropism ◽  
Neural Models ◽  
The Central Nervous System ◽  
Induced Pluripotent ◽  
The Brain

Infections with the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are often associated with neurological complications. Evidence suggests that SARS-CoV-2 enters the brain via the olfactory nerve; however, SARS-CoV-2 is only rarely detected in the central nervous system of COVID-19 patients.

scholarly journals MicroRNA profiling of mouse liver in response to DENV-1 infection by deep sequencing

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6697 ◽  
Author(s):  
Lian Yih Pong ◽  
Sinikka Parkkinen ◽  
Amreeta Dhanoa ◽  
Han Ming Gan ◽  
Indeevari Abisheka Chiharu Wickremesinghe ◽  
...  
Keyword(s):  
Immune Responses ◽  
Infected Mouse ◽  
Deep Sequencing ◽  
Molecular Mechanisms ◽  
Fold Change ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Mirna Sequencing

BackgroundDengue caused by dengue virus (DENV) serotypes −1 to −4 is the most important mosquito-borne viral disease in the tropical and sub-tropical countries worldwide. Yet many of the pathophysiological mechanisms of host responses during DENV infection remain largely unknown and incompletely understood.MethodsUsing a mouse model, the miRNA expressions in liver during DENV-1 infection was investigated using high throughput miRNA sequencing. The differential expressions of miRNAs were then validated by qPCR, followed by target genes prediction. The identified miRNA targets were subjected to gene ontology (GO) annotation and pathway enrichment analysis to elucidate the potential biological pathways and molecular mechanisms associated with DENV-1 infection.ResultsA total of 224 and 372 miRNAs out of 433 known mouse miRNAs were detected in the livers of DENV-1-infected and uninfected mice, respectively; of these, 207 miRNAs were present in both libraries. The miR-148a-3p and miR-122-5p were the two most abundant miRNAs in both groups. Thirty-one miRNAs were found to have at least 2-fold change in upregulation or downregulation, in which seven miRNAs were upregulated and 24 miRNAs were downregulated in the DENV-1-infected mouse livers. The miR-1a-3p was found to be the most downregulated miRNA in the DENV-1-infected mouse livers, with a significant fold change of 0.10. To validate the miRNA sequencing result, the expression pattern of 12 miRNAs, which were highly differentially expressed or most abundant, were assessed by qPCR and nine of them correlated positively with the one observed in deep sequencing.In silicofunctional analysis revealed that the adaptive immune responses involving TGF-beta, MAPK, PI3K-Akt, Rap1, Wnt and Ras signalling pathways were modulated collectively by 23 highly differentially expressed miRNAs during DENV-1 infection.ConclusionThis study provides the first insight into the global miRNA expressions of mouse livers in response to DENV-1 infectionin vivoand the possible roles of miRNAs in modulating the adaptive immune responses during DENV-1 infection.

scholarly journals A Combined Adjuvant TF–Al Consisting of TFPR1 and Aluminum Hydroxide Augments Strong Humoral and Cellular Immune Responses in Both C57BL/6 and BALB/c Mice

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1408
Author(s):  
Qiao Li ◽  
Zhihua Liu ◽  
Yi Liu ◽  
Chen Liang ◽  
Jiayi Shu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Inbred Mouse ◽  
Effective Vaccine ◽  
Mouse Strains ◽  
Cellular Immune Responses ◽  
Recombinant Hbsag ◽  
Cellular Immune

TFPR1 is a novel adjuvant for protein and peptide antigens, which has been demonstrated in BALB/c mice in our previous studies; however, its adjuvanticity in mice with different genetic backgrounds remains unknown, and its adjuvanticity needs to be improved to fit the requirements for various vaccines. In this study, we first compared the adjuvanticity of TFPR1 in two commonly used inbred mouse strains, BALB/c and C57BL/6 mice, in vitro and in vivo, and demonstrated that TFPR1 activated TLR2 to exert its immune activity in vivo. Next, to prove the feasibility of TFPR1 acting as a major component of combined adjuvants, we prepared a combined adjuvant, TF–Al, by formulating TFPR1 and alum at a certain ratio and compared its adjuvanticity with that of TFPR1 and alum alone using OVA and recombinant HBsAg as model antigens in both BALB/c and C57BL/6 mice. Results showed that TFPR1 acts as an effective vaccine adjuvant in both BALB/c mice and C57BL/6 mice, and further demonstrated the role of TLR2 in the adjuvanticity of TFPR1 in vivo. In addition, we obtained a novel combined adjuvant, TF–Al, based on TFPR1, which can augment antibody and cellular immune responses in mice with different genetic backgrounds, suggesting its promise for vaccine development in the future.

scholarly journals Psychoneuroimmunoendocrinology and Immune Homeostasis: Gut-brain Axis, Obesity and Cognitive Function

2020 ◽  
Vol 6 (12) ◽  
pp. 124-154
Author(s):  
S. Bulgakova ◽  
N. Romanchuk ◽  
O. Pomazanova
Keyword(s):  
Artificial Intelligence ◽  
Health Care ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Cognitive Functions ◽  
Immune Homeostasis ◽  
Obesity And Diabetes ◽  
Human Immune ◽  
The Cross ◽  
The Brain

The new competencies of psychoneuroimmunoendocrinology and psychoneuroimmunology play a strategic role in interdisciplinary science and interdisciplinary planning and decision-making. The introduction of multi-vector neurotechnologies of artificial intelligence and the principles of digital health care will contribute to the development of modern neuroscience and neuromarketing. The availability of innovative technologies, such as next-generation sequencing and correlated bioinformatics tools, allows deeper investigation of the cross-network relationships between the microbiota and human immune responses. Immune homeostasis is the balance between immunological tolerance and inflammatory immune responses — a key feature in the outcome of health or disease. A healthy microbiota is the qualitative and quantitative ratio of diverse microbes of individual organs and systems, maintaining the biochemical, metabolic and immune equilibrium of the macroorganism necessary to preserve human health. Functional foods, healthy biomicrobiota, healthy lifestyle and controlled protective environmental effects, artificial intelligence and electromagnetic information load/overload are responsible for the work of the human immune system and its ability to respond to pandemic attacks in a timely manner. Obesity continues to be one of the main problems of modern health care due to its high prevalence and polymorbidity. In addition to cardiometabolic diseases, lesions of the musculoskeletal system, obese individuals show impaired cognitive functions, have a high risk of developing depression and anxiety. The gut microbiota mediates between environmental influences (food, lifestyle) and the physiology of the host, and its change may partially explain the cross-link between the above pathologies. It is known that Western eating patterns are the main cause of the obesity epidemic, which also contributes to dysbiotic drift of the gut microbiota, which in turn contributes to the development of complications associated with obesity. Experimental studies in animal models and, to a lesser extent in humans, show that microbiota is associated with obesity and may contribute to the endocrine, neurochemical and development of systemic inflammation underlying obesity itself and related diseases. Nevertheless, a number of questions remain at present. Modeling the microbiota-gut-brain axis, provides the brain with information from the gut not only through the nervous system but also through a continuous stream of microbial, endocrine, metabolic and immune messages. The communication network provides important keys to understanding how obesity and diabetes can affect the brain by provoking neuropsychiatric diseases. The literature review is devoted to the analysis of data on the relationship of the gut-brain axis, obesity and cognitive functions, immune homeostasis and new competencies: psychoneuroimmunology and psychoneuroimmunoendocrinology.

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