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Type 3 Interferon

Midori Kjellin, Terése Wesslén, Erik Löfblad, Johan Lennerstrand, Anders Lannergård
BACKGROUND: The clinical experience with protease-inhibitor (PI) triple regimen appears disappointing regarding effect, side effects, high work load, and costs. This real-world study evaluates baseline and emerging resistance-associated substitutions (RASs) and their significance for treatment outcome. METHOD: Thirty-six genotype 1a/b patients treated according to Swedish recommendations during 2011-2013 with triple therapy including pegylated interferon and ribavirin in combination with a protease-inhibitor, either boceprevir (BOC) or telaprevir (TVR), were retrospectively evaluated...
March 14, 2018: Upsala Journal of Medical Sciences
M Nasiri, B Geramizadeh, S H Nabavizadeh, S A Male-Hosseini, M H Karimi, I Saadat
Background: Interferon regulatory factors (IRFs) can play a critical role in the regulation of many facets of innate and adaptive immune responses through transcriptional activation of type I interferons, other proinflammatory cytokines, and chemokines. However, their roles in transplantation immunity still remain to be elucidated. Objective: To evaluate the time course of mRNA expression of all 9 members of IRFs family of transcription factors during liver allograft acute rejection...
2018: International Journal of Organ Transplantation Medicine
Hanaa Ahmed-Hassan, Mohamed Sarjoon Abdul-Cader, Upasama De Silva Senapathi, Maha Ahmed Sabry, Eman Hamza, Eva Nagy, Shayan Sharif, Mohamed Faizal Abdul-Careem
BACKGROUND: Toll like receptor (TLR) 3 is a critically important innate pattern recognizing receptor that senses many viral infections. Although, it has been shown that double stranded (ds) RNA can be used for the stimulation of TLR3 signaling pathway in a number of host-viral infection models, it's effectiveness as an antiviral agent against low pathogenic avian influenza virus (LPAIV) needs further investigation. METHODS: In this study, first, we delivered TLR3 ligand, dsRNA, in ovo at embryo day (ED)18 since in ovo route is routinely used for vaccination against poultry viral and parasitic infections and infected with H4N6 LPAIV 24-h post-treatment...
March 12, 2018: Virology Journal
Samuel C Cerps, Mandy Menzel, Irma Mahmutovic Persson, Leif Bjermer, Hamid Akbarshahi, Lena Uller
Defective production of antiviral interferon (IFN)-β is thought to contribute to rhinovirus-induced asthma exacerbations. These exacerbations are associated with elevated lung levels of lactate dehydrogenase (LDH), indicating occurrence of cell necrosis. We thus hypothesized that reduced lung IFN-β could contribute to necrotic cell death in a model of asthma exacerbations. Wild-type and IFN-β-/- mice were given saline or house dust mite (HDM) intranasally for 3 weeks to induce inflammation. Double-stranded RNA (dsRNA) was then given for additional 3 days to induce exacerbation...
March 9, 2018: Scientific Reports
Ariadne Androulidaki, Laurens Wachsmuth, Apostolos Polykratis, Manolis Pasparakis
Type 1 diabetes (T1D) is caused by the autoimmune destruction of the insulin-producing pancreatic beta cells. While the role of adaptive immunity has been extensively studied, the role of innate immune responses and particularly of Toll- like Receptor (TLR) signaling in T1D remains poorly understood. Here we show that myeloid cell-specific MyD88 deficiency considerably protected mice from the development of streptozotocin (STZ)-induced diabetes. The protective effect of MyD88 deficiency correlated with increased expression of the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) in pancreatic lymph nodes from STZ-treated mice and in bone marrow-derived dendritic cells (BMDC) stimulated with apoptotic cells...
2018: PloS One
Josefine Radke, Randi Koll, Corinna Preuße, Debora Pehl, Kremena Todorova, Constanze Schönemann, Yves Allenbach, Eleonora Aronica, Marianne de Visser, Frank L Heppner, Joachim Weis, Soroush Doostkam, Thierry Maisonobe, Olivier Benveniste, Hans-Hilmar Goebel, Werner Stenzel
Objective: To study the B-cell content, organization, and existence of distinct B-cell subpopulations in relation to the expression of type 1 interferon signature related genes in dermatomyositis (DM). Methods: Evaluation of skeletal muscle biopsies from patients with adult DM (aDM) and juvenile DM (jDM) by histology, immunohistochemistry, electron microscopy, and quantitative reverse-transcription PCR. Results: We defined 3 aDM subgroups-classic (containing occasional B cells without clusters), B-cell-rich, and follicle-like aDM-further elucidating IM B-lymphocyte maturation and immunity...
May 2018: Neurology® Neuroimmunology & Neuroinflammation
Chong Huang, Xiao-Hua Yu, Xi-Long Zheng, Xiang Ou, Chao-Ke Tang
Macrophage autophagy contributes to the hydrolysis of cholesteryl ester into free cholesterol mainly for ATP-binding cassette transporter A1 (ABCA1)-dependent efflux. Interferon-stimulated gene 15 (ISG15) has been shown to regulate autophagy in multiple types of cells. The present study aimed to examine the effects of ISG15 on autophagy and cholesterol efflux in THP-1 macrophage-derived foam cells and to explore the underlying molecular mechanisms. Our results showed that overexpression of ISG15 promoted autophagy and cholesterol efflux and inhibited lipid accumulation without impact on ABCA1 expression...
March 5, 2018: European Journal of Pharmacology
Zhulong Hu, Yuang Wang, Qiaopeng Tang, Xiaodan Yang, Yali Qin, Mingzhou Chen
Viral invasion triggers the activation of the host antiviral response. Besides the innate immune response, stress granules (SGs) also act as an additional defense response to combat viral replication. However, many viruses have evolved various strategies to suppress SG formation to facilitate their own replication. Here, we show that viral mRNAs derived from human parainfluenza virus type 3 (HPIV3) infection induce SG formation in an eIF2α phosphorylation- and PKR-dependent manner in which viral mRNAs are sequestered and viral replication is inhibited independent of the interferon signaling pathway...
March 8, 2018: PLoS Pathogens
P Zhang, W Zhang, D Zhang, M Wang, R Aprecio, N Ji, O Mohamed, Y Li, Y Ding, Q Wang
BACKGROUND AND OBJECTIVE: Periodontitis is an increasingly prevalent complication of diabetes mellitus (known as diabetes mellitus-associated periodontitis), and 25-hydroxyvitamin D3 (25VD3 ) was recently found to be a critical regulator of innate immunity in this disease, but the underlying mechanisms remain poorly understood. T-cell protein tyrosine phosphatase non-receptor type 2 (PTPN2) is a potential downstream protein of the 25VD3 /vitamin D receptor pathway. The aim of this study was to investigate the regulation of PTPN2 in periodontal inflammation in diabetes mellitus-associated periodontitis...
March 8, 2018: Journal of Periodontal Research
Rose M Langsjoen, Sherry L Haller, Chad J Roy, Heather Vinet-Oliphant, Nicholas A Bergren, Jesse H Erasmus, Jill A Livengood, Tim D Powell, Scott C Weaver, Shannan L Rossi
Chikungunya virus (CHIKV) is a reemerging arbovirus capable of causing explosive outbreaks of febrile illness, polyarthritis, and polyarthralgia, inflicting severe morbidity on affected populations. CHIKV can be genetically classified into 3 major lineages: West African (WA); East, Central, and South African (ECSA); Indian Ocean (IOL); and Asian. Additionally, the Indian Ocean (IOL) sublineage emerged within the ECSA clade and the Asian/American sublineage emerged within the Asian clade. While differences in epidemiological and pathological characteristics among outbreaks involving different CHIKV lineages and sublineages have been suggested, few targeted investigations comparing lineage virulence levels have been reported...
March 6, 2018: MBio
Lijie Gao, Yunqi Wang, Yi Li, Ya Dong, Aimin Yang, Jie Zhang, Fengying Li, Rongqiang Zhang
Objectives Comprehensive bioinformatics analyses were performed to explore the key biomarkers in response to HIV infection of CD4+ and CD8+ T cells. Methods The numbers of CD4+ and CD8+ T cells of HIV infected individuals were analyzed and the GEO database (GSE6740) was screened for deferentially expressed genes (DEGs) in HIV infected CD4+ and CD8+ T cells. Gene Ontology enrichment, KEGG pathway analyses and protein-protein interaction (PPI) network were performed to identify the key pathway and core proteins in anti-HIV virus process of CD4+ and CD8+ T cells...
March 6, 2018: Journal of Medical Virology
J Papinska, H Bagavant, G B Gmyrek, M Sroka, S Tummala, K A Fitzgerald, U S Deshmukh
Sjögren syndrome (SS), a chronic autoimmune disorder causing dry mouth, adversely affects the overall oral health in patients. Activation of innate immune responses and excessive production of type I interferons (IFNs) play a critical role in the pathogenesis of this disorder. Recognition of nucleic acids by cytosolic nucleic acid sensors is a major trigger for the induction of type I IFNs. Upon activation, cytosolic DNA sensors can interact with the stimulator of interferon genes (STING) protein, and activation of STING causes increased expression of type I IFNs...
March 1, 2018: Journal of Dental Research
Frans Eberth Costa Andrade, Mab Pereira Corrêa, Alexandre Dantas Gimenes, Myrna Serapião Dos Santos, Mauro Campos, Roger Chammas, José Álvaro Pereira Gomes, Cristiane Damas Gil
AIMS: To evaluate galectin-3 (Gal-3), a β-galactoside binding protein, as a possible biomarker in ocular allergy and further investigated the role of endogenous Gal-3 in a murine model of ovalbumin (OVA)-induced allergic conjunctivitis (AC). METHODS: Conjunctival impression cytology specimens from control and patients with severe vernal keratoconjunctivitis, treated or untreated, were used to evaluate Gal-3 expression by immunocytochemistry. To investigate the mechanism of action of Gal-3, OVA-immunised BALB/c male wild-type (WT) and Gal-3 null (Gal-3-/- ) mice were challenged with eye drops containing OVA on days 14-16 with a subset of animals pretreated with 0...
March 3, 2018: British Journal of Ophthalmology
Min Cheng, Yuqiang Niu, Jingjing Fan, Xiaojing Chi, Xiuying Liu, Wei Yang
Induction of interferons (IFNs) is a central event of antiviral innate immunity. As crucial post-transcriptional regulators, microRNAs (miRNAs) are important for IFN-mediated host defense. Although screening has indicated a substantial number of miRNAs to be differentially expressed after IFN stimulation, the detailed mechanisms of these miRNAs in the antiviral response is underexplored and of great significance. Here, we show that hsa-miR-1225-3p is specifically downregulated by type I IFN through IFN/JAK/STAT signaling pathway...
March 1, 2018: Journal of Biological Chemistry
Jose L Gomez, Maria P Diaz, Gustavo Nino, Clemente J Britto
BACKGROUND: Asthma exacerbations are an important cause of morbidity in asthma. Respiratory infections are often involved in asthma exacerbations in both children and adults. Some individuals with asthma have increased susceptibility to viral infections and as a result increased rates of asthma exacerbations. We sought to identify a transcriptomic signature in the blood associated with asthma exacerbations triggered by respiratory infections (AETRI) and determine its association with increased risk for asthma exacerbations...
February 27, 2018: BMC Medical Genomics
Liang Xu, Tian Qiu, Yudong Wang, Yan Chen, Weiwei Cheng
In the present study, the mechanisms underlying the pathogenesis of unexplained recurrent spontaneous abortion (URSA) were explored. The protein and mRNA expression of two C-type lectin-like receptors (CLRs), namely dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and mannose receptor (MR), and two Toll-like receptors (TLRs), namely TLR2 and TLR4, in the decidua and dendritic cells (DCs) was compared between URSA patients and normal controls. URSA patients had significantly lower protein and mRNA expression of DC-SIGN and significantly higher expression of TLR2 and TLR4 in decidual tissues compared with normal controls...
August 2017: Reproduction, Fertility, and Development
Sonia Zeggar, Katsue S Watanabe, Sanae Teshigawara, Sumie Hiramatsu, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Yoshinori Matsumoto, Tomoko Kawabata, Ken-Ei Sada, Toshiro Niki, Mitsuomi Hirashima, Jun Wada
OBJECTIVE: In systemic lupus erythematosus (SLE), an autoimmune disease associated with multiple organ involvements, lupus nephritis determines prognosis and arthritis impairs quality of life of patients. Galectin-9 (Gal-9, Lgals9) is a β-galactoside binding lectin and the attempts for its clinical application have been made in autoimmune diseases, since recombinant Gal-9 as a ligand for Tim-3 induces apoptosis in activated CD4+ Tim-3+ Th1 cell. We investigated wethere the deficiency of Lgals9 is beneficial or deleterious in lupus mice models...
February 26, 2018: Arthritis & Rheumatology
Radiana T Trifonova, Natasha S Barteneva
Imaging flow cytometry (IFC) has become a powerful tool for studying the activation of transcriptional factors in heterogeneous cell populations in high-content imaging mode. With considerable interest to the clinical development of IFC, the question becomes how we can accelerate its application to solid tissues. We developed the first IFC-based procedure to quantify the nuclear translocation of interferon regulatory factor (IRF) 3, an important measure of induction of type I interferon antiviral response, in primary human immune cells including in solid tissues...
2018: Methods in Molecular Biology
Yan-Hong Yong, Shao-Feng Liu, Guo-Hong Hua, Ru-Min Jia, Ravi Gooneratne, Yun-Tao Zhao, Ming Liao, Xiang-Hong Ju
Induction of the innate immune pathways is critical for early anti-viral defense. How geese recognize viral molecules and activate these pathways is not well understood. In mammals, Toll-like receptor 3 (TLR3) recognizes double-stranded RNA. Activation of TLR3 induces the activation of NF-кB and the production of type-I interferon. In this study, the goose TLR3 gene was cloned using rapid amplification of cDNA ends. Goose TLR3 encoded an 896-amino-acid protein, containing a signal secretion peptide, 14 extracellular leucine-rich repeat domains, a transmembrane domain, a Toll/interleukin-1 receptor signaling domain, and shared 46...
March 2018: Veterinary Immunology and Immunopathology
Ryo Okada, Xinwen Zhang, Yuka Harada, Zhou Wu, Hiroshi Nakanishi
OBJECTIVE: The objective of this study is to investigate the role of cathepsin H (CatH), a lysosomal cysteine protease, in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. METHODS: EAE was induced in CatH-deficient mice (CatH-/- ) and wild-type littermates (+/+) using myelin oligodendrocyte glycoprotein (MOG) 35-55. The effects of CatH deficiency were determined by clinical scoring, mRNA expression levels of Tbx21, Rorc and FoxP3, protein levels of poly(I:C)-induced toll-like receptor 3 (TLR3) and phosphorylation of IRF3, and secretion of interferon-β (IFN-β) by splenocytes...
February 22, 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
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