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Peter Hart, Alastair Copland, Gil Reynolds Diogo, Shane Harris, Ralf Spallek, Wulf Oehlmann, Mahavir Singh, Juan Basile, Martin Rottenberg, Matthew John Paul, Rajko Reljic
Tuberculosis (TB) is the leading cause of death from infectious disease, and the current vaccine, Bacillus Calmette-Guerin (BCG), is inadequate. Nanoparticles (NPs) are an emerging vaccine technology, with recent successes in oncology and infectious diseases. NPs have been exploited as antigen delivery systems and also for their adjuvantic properties. However, the mechanisms underlying their immunological activity remain obscure. Here, we developed a novel mucosal TB vaccine (Nano-FP1) based upon yellow carnauba wax NPs (YC-NPs), coated with a fusion protein consisting of three Mycobacterium tuberculosis (Mtb) antigens: Acr, Ag85B, and HBHA...
March 7, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Chamilani Nikapitiya, S H S Dananjaya, B C J De Silva, Gang-Joon Heo, Chulhong Oh, Mahanama De Zoysa, Jehee Lee
Chitosan nanoparticles (CNPs) were synthesized by ionic gelation method and its immunomodulatory properties were investigated in zebrafish larvae. Average particle size and zeta potential were 181.2 nm and +37.2 mv, respectively. Initially, toxicity profile was tested in zebrafish embryo at 96 h post fertilization (hpf) stage using medium molecular weight chitosan (MMW-C) and CNPs. At 5 μg/mL, the hatching rate was almost similar in both treatments, however, the survival rate was lower in MMW-C compared to CNPs exposure, suggesting that toxicity effect of CNPs in hatched larvae was minimal at 5 μg/mL compared to MMW-C...
March 3, 2018: Fish & Shellfish Immunology
Rahul Krishnan, Jeena K, Zahoor Mushtaq, K U Shyam, Pani Prasad Kurcheti
The innate immune signaling adapter, Mitochondrial antiviral signaling protein (MAVS) coordinates the signals received from two independent RLRs (RIG-1 and MDA5) to induce IFN & interferon stimulatory genes (ISGs). In the present study, we report identification of an orthologue of MAVS from Lates calcarifer (LcMAVS) and its functional role in piscine RLR signaling. The LcMAVS-cDNA was cloned into pcDNA and transfected into SISS cells. LcMAVS was detected to be a 61KDa protein in western blot. Confocal microscopy demonstrated the mitochondrial localization of LcMAVS...
March 3, 2018: Fish & Shellfish Immunology
Tomio Matsumura, Shigeaki Hida, Masato Kitazawa, Chifumi Fujii, Akira Kobayashi, Michiko Takeoka, Shun-Ichiro Taniguchi, Shin-Ichi Miyagawa
Fascin1 is an actin-bundling protein involved in cancer cell migration and has recently been shown also to have roles in virus-mediated immune cell responses. Because viral infection has been shown to activate immune cells and to induce IFN-β expression in human cancer cells, we evaluated the effects of fascin1 on virus-dependent signaling via the membrane- and actin-associated protein retinoic acid-inducible gene I (RIG-I) in colon cancer cells. We knocked down fascin1 expression with shRNA retrovirally transduced into a DLD-1 colon cancer and L929 fibroblast-like cell lines and used luciferase reporter assays and co-immunoprecipitation to identify fascin1 targets...
March 1, 2018: Journal of Biological Chemistry
Iliana Georgana, Rebecca P Sumner, Greg J Towers, Carlos Maluquer de Motes
Cytosolic recognition of DNA has emerged as a critical cellular mechanism of host immune activation upon pathogen invasion. The central cytosolic DNA sensor cGAS activates STING, which is phosphorylated, dimerises and translocates from the ER to a perinuclear region to mediate IRF-3 activation. Poxviruses are dsDNA viruses replicating in the cytosol and hence likely to trigger cytosolic DNA sensing. Here we investigated the activation of innate immune signalling by 4 different strains of the prototypic poxvirus vaccinia virus (VACV) in a cell line proficient in DNA sensing...
February 28, 2018: Journal of Virology
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
Young-Su Yi, Jinlong Jian, Elena Gonzalez-Gugel, Yong-Xiang Shi, Qingyun Tian, Wenyu Fu, Aubryanna Hettinghouse, Wenhao Song, Ronghan Liu, Michun He, Huabing Qi, Jing Yang, Xiaolan Du, GuoZhi Xiao, Lin Chen, Chuan-Ju Liu
p204, a murine member of an interferon-inducible p200 family, was reported to recognize intracellular viral and bacterial DNAs, however, its role in the innate immunity in vivo remains unknown due to the lack of p204-deficient animal models. In this study we first generated the p204-/- mice. Unexpectedly, p204 deficiency led to significant defect in extracellular LPS signaling in macrophages, as demonstrated by dramatic reductions of LPS-mediated IFN-β and pro-inflammatory cytokines. The serum levels of IFN-β and pro-inflammatory cytokines were also significantly reduced in p204-/- mice following LPS challenge...
February 16, 2018: EBioMedicine
Dörthe Masemann, Rafael Leite Dantas, Siarhei Sitnik, Tanja Schied, Carolin Nordhoff, Stephan Ludwig, Viktor Wixler
FHL2 is a multifunctional adaptor protein with fine-tuning adjustment properties. It acts as a regulator of signaling cascades but also as a cofactor of transcription and controls several anti-inflammatory immune responses. Recently, we described FHL2 as a novel regulator of influenza A virus propagation. We have shown that in vitro FHL2 restricts viral replication by accelerating the IRF-3-dependent transcription of the Ifnb1 gene. In this work, we unraveled an ambiguous role of FHL2 during influenza A virus infection in vivo...
February 17, 2018: American Journal of Pathology
Andra Banete, Kyle Seaver, Devyani Bakshi, Katrina Gee, Sameh Basta
Nearly a decade ago, an endoplasmic reticulum (ER) adaptor protein called stimulator of interferon genes (STING) was found to be critical in the induction of type I IFN production in response to DNA virus infection. STING functions by sensing cytoplasmic DNA and activates key transcription factors, including IFN regulatory factor (IRF)-3 and IRF7, to initiate type I IFN expression. Type I IFNs are vital in immunity against viral infections and can influence cancer cell proliferation, migration, and apoptosis...
February 12, 2018: Journal of Leukocyte Biology
Sylwia Moskwa, Wojciech Piotrowski, Jerzy Marczak, Małgorzata Pawełczyk, Anna Lewandowska-Polak, Marzanna Jarzębska, Małgorzata Brauncajs, Anna Głobińska, Paweł Górski, Nikolaos G Papadopoulos, Michael R Edwards, Sebastian L Johnston, Marek L Kowalski
PURPOSE: In order to gain an insight into determinants of reported variability in immune responses to respiratory viruses in human bronchial epithelial cells (HBECs) from asthmatics, the responses of HBEC to viral infections were evaluated in HBECs from phenotypically heterogeneous groups of asthmatics and in healthy controls. METHODS: HBECs were obtained during bronchoscopy from 10 patients with asthma (6 atopic and 4 non-atopic) and from healthy controls (n=9) and grown as undifferentiated cultures...
March 2018: Allergy, Asthma & Immunology Research
Y S Abulfadl, N N El-Maraghy, Aa Eissa Ahmed, S Nofal, Y Abdel-Mottaleb, O A Badary
Alzheimer's disease (AD) is characterized by a robust inflammatory response elicited by the accumulation and deposition of amyloid-β (Aβ) within the brain. Aβ induces detrimental inflammatory responses through toll-like receptors (TLRs) signaling pathway. Thymoquinone (TQ), the main active constituent of Nigella sativa oil, has been reported by several previous studies for its potent anti-inflammatory effect. The aim of this study is to elucidate the effect of TQ in improving learning and memory, using a rat model of AD induced by a combination of aluminum chloride (AlCl 3 ) and d-galactose (d-Gal)...
January 1, 2018: Human & Experimental Toxicology
Yingnan Wang, Xing Qin, Xueqin Zhu, Wanjun Chen, Jianjun Zhang, Wantao Chen
No abstract text is available yet for this article.
January 25, 2018: Oral Oncology
Xiao-Bo Yang, Hong Jiang, Yao Shi
Although the pathogenesis of liver ischemia-reperfusion (IR) has been well reported, its molecular mechanism is not fully understood. Suppressor of IKKε (SIKE1) is an interaction partner for Inhibitor of κB Kinase ε (IKKε), a negative modulator of the interferon pathway. In the study, we explored the effects of SIKE1 on liver IR injury in the wild type (WT) and SIKE1-knockout (KO) mice. The findings indicated that after IR operation, reduced SIKE1 expressions were observed in liver of mice. And lipopolysaccharide (LPS) time-dependently decreased SIKE1 mRNA and protein levels in liver cells...
January 20, 2018: Biochemical and Biophysical Research Communications
Hamid Akbarshahi, Mandy Menzel, Sangeetha Ramu, Irma Mahmutovic Persson, Leif Bjermer, Lena Uller
BACKGROUND: Impaired antiviral interferon expression may be involved in asthma exacerbations commonly caused by rhinovirus infections. Allergy is a known risk factor for viral-induced asthma exacerbation, but little is known whether allergens may affect interferon responses. OBJECTIVE: Our hypothesis is that house dust mite (HDM) impairs viral stimulus-induced antiviral signalling. METHODS: Experimental asthma exacerbations were produced in vitro in human bronchial epithelial cells (HBECs) and in mice by using sequential challenges with HDM and a viral infection mimic, Poly(I:C)...
January 10, 2018: Allergy
Yingnan Wang, Xing Qin, Xueqin Zhu, Wanjun Chen, Jianjun Zhang, Wantao Chen
OBJECTIVE: To examine the effects of oral cancer-derived exosomes (OCEXs) on natural killer (NK) cells and to explore the underlying mechanism. MATERIALS AND METHODS: OCEXs were isolated from the cell culture supernatant of oral cancer (OC) cells using ultrafiltration and affinity chromatography and were identified using electron microscopy, nanoparticle tracking analysis (NTA) and immunoblotting. The effects of OCEXs on NK cells were analyzed using laser scanning confocal microscopy and several functional assays of NK cells...
January 2018: Oral Oncology
Aaron F Carlin, Emily M Plummer, Edward A Vizcarra, Nicholas Sheets, Yunichel Joo, William Tang, Jeremy Day, Jay Greenbaum, Christopher K Glass, Michael S Diamond, Sujan Shresta
Interferon-regulatory factors (IRFs) are a family of transcription factors (TFs) that translate viral recognition into antiviral responses, including type I interferon (IFN) production. Dengue virus (DENV) and other clinically important flaviviruses are suppressed by type I IFN. While mice lacking the type I IFN receptor (Ifnar1(-/-)) succumb to DENV infection, we found that mice deficient in three transcription factors controlling type I IFN production (Irf3(-/-)Irf5(-/-)Irf7(-/-) triple knockout [TKO]) survive DENV challenge...
November 7, 2017: Cell Reports
Lu-Lu Wang, Lan-Bo Zhou, Jin Shu, Nan-Nan Li, Hui-Wen Zhang, Rui Jin, Li-Li Zhuang, Guo-Ping Zhou
Interferon regulatory factor 3 (IRF-3) is an important transcription factor for interferon genes. Although its functional activation by viral infection has been widely explicated, the regulatory mechanism of IRF-3 gene expression in cancer cells is poorly understood. In this study, we demonstrated treatment of lung adenocarcinoma A549 cells with trichostatin A (TSA) and valproic acid (VPA), two different classes of histone deacetylase inhibitors, strongly stimulated IRF-3 gene expression. Truncated and mutated IRF-3 promoter indicated that a specific GATA-1 element was responsible for TSA-induced activation of IRF-3 promoter...
September 29, 2017: Oncotarget
Taku Shimada, Tadaatsu Imaizumi, Kyogo Shirai, Tetsuya Tatsuta, Toshiro Kimura, Ryo Hayakari, Hidemi Yoshida, Tomoh Matsumiya, Hiroshi Kijima, Hiroki Mizukami, Kenichi Hakamada
Biliary atresia (BA) is a disease of the newborn that is characterized by progressive, inflammatory and sclerosing cholangiopathy. Innate immune responses to viral components are thought to be involved in the pathogenesis of BA. It is also reported that some chemokines, such as CCL5, are possibly involved in the pathogenesis of experimental animal model of BA. We treated human biliary epithelial HuCCT1 cells with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA (dsRNA) which mimics viral RNA, and analyzed the CCL5 expression by quantitative reverse transcription-PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA)...
2017: Biomedical Research
Satheesha Avunje, Sung-Ju Jung
The stimulation of immune genes by polyinosinic:polycytidylic acid (poly (I:C)) and imiquimod in olive flounder (Paralichthys olivaceus) and their role in control of viral haemorrhagic septicaemia virus (VHSV) infection were examined. Poly (I:C) (100 μg/fish) treated olive flounder had very low mortality (5%) post VHSV infection, while the imiquimod treated group had 65% and 85% mortality at a dose of 100 μg/fish and 50 μg/fish, respectively. Though the imiquimod treated group had high mortality, it was lower than the untreated group, which had 90% mortality...
October 18, 2017: Fish & Shellfish Immunology
Xiaowen Xu, Meifeng Li, Zhen Wu, Haizhou Wang, Liqiang Wang, Keyi Huang, Xiancheng Liu, Qunhao Hou, Gang Lin, Chengyu Hu
IFN regulatory factor (IRF)3 is a central regulator for IFN-β expression in different types of pathogenic infections. Mammals have various pathogenic sensors that are involved in monitoring pathogen intrusions. These sensors can trigger IRF3-mediated antiviral responses through different pathways. Endoplasmic reticulum-associated proteins stimulator of IFN gene (STING) and zinc finger DHHC-type containing 1 (ZDHHC1) are critical mediators of IRF3 activation in response to viral DNA infections. In this study, grass carp STING and ZDHHC1 were found to have some similar molecular features and subcellular localization, and both were upregulated upon stimulation with polyinosinic:polycytidylic acid, B-DNA, or Z-DNA...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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