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https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#1
Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R Porembka, Jayanthi Lea, Arthur E Frankel, Yang-Xin Fu, Zhijian J Chen, Jinming Gao
The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes...
April 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28435890/gene-expression-profile-of-human-cytokines-in-response-to-burkholderia-pseudomallei-infection
#2
Shivankari Krishnananthasivam, Harindra Darshana Sathkumara, Enoka Corea, Mohan Natesan, Aruna Dharshan De Silva
Melioidosis is an underreported infectious disease, caused by the Gram-negative bacterium Burkholderia pseudomallei. Understanding the disease susceptibility and pathogenesis is crucial for developing newer diagnostic and therapeutic strategies for this life-threatening infection. In this study, we aimed to analyze the gene expression levels of important cytokines in melioidosis patients and establish useful correlates with disease biomarkers compared to cases of sepsis infection caused by other pathogens and healthy individuals...
March 2017: MSphere
https://www.readbyqxmd.com/read/28432378/advances-in-anti-viral-immune-defence-revealing-the-importance-of-the-ifn-jak-stat-pathway
#3
REVIEW
Nicola Raftery, Nigel J Stevenson
Interferon-alpha (IFN-α) is a potent anti-viral cytokine, critical to the host immune response against viruses. IFN-α is first produced upon viral detection by pathogen recognition receptors. Following its expression, IFN-α embarks upon a complex downstream signalling cascade called the JAK/STAT pathway. This signalling pathway results in the expression of hundreds of effector genes known as interferon stimulated genes (ISGs). These genes are the basis for an elaborate effector mechanism and ultimately, the clearance of viral infection...
April 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28428785/interferon-gamma-induces-changes-in-natural-killer-nk-cell-ligand-expression-and-alters-nk-cell-mediated-lysis-of-pediatric-cancer-cell-lines
#4
Arianexys Aquino-López, Vladimir V Senyukov, Zlatko Vlasic, Eugenie S Kleinerman, Dean A Lee
Natural killer (NK) cells have therapeutic potential for cancer due to their capacity for targeting tumor cells without prior sensitization. Our laboratory has developed an NK cell expansion protocol that generates large quantities of NK cells for therapeutic infusion that secret 20 times the amount of interferon gamma (IFNγ) than resting NK cells. IFNγ can upregulate major histocompatibility complex (MHC)-class I, an inhibitory ligand for NK cells, but can also upregulate intercellular adhesion molecule 1 (ICAM-1) which promotes NK:target cell interaction for an efficient lysis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28426803/dendritic-cell-maturation-but-not-type-i-interferon-exposure-restricts-infection-by-htlv-1-and-viral-transmission-to-t-cells
#5
Gergès Rizkallah, Sandrine Alais, Nicolas Futsch, Yuetsu Tanaka, Chloé Journo, Renaud Mahieux, Hélène Dutartre
Human T lymphotropic Virus type 1 (HTLV-1) is the etiological agent of Adult T cell Leukemia/Lymphoma (ATLL) and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Both CD4+ T-cells and dendritic cells (DCs) infected with HTLV-1 are found in peripheral blood from HTLV-1 carriers. We previously demonstrated that monocyte-derived IL-4 DCs are more susceptible to HTLV-1 infection than autologous primary T-cells, suggesting that DC infection precedes T-cell infection. However, during blood transmission, breast-feeding or sexual transmission, HTLV-1 may encounter different DC subsets present in the blood, the intestinal or genital mucosa respectively...
April 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28426273/preclinical-development-of-bcg-hiva-2auxo-int-harboring-an-integrative-expression-vector-for-a-hiv-tb-pediatric-vaccine-enhancement-of-stability-and-specific-hiv-1-t-cell-immunity
#6
Aakash Mahant, Narcís Saubi, Yoshiki Eto, Núria Guitart, Josep M ª Gatell, Tomáš Hanke, Joan Joseph
One of the critical issues that should be addressed in the development of a BCG-based HIV vaccine is genetic plasmid stability. Therefore, to address this issue we have considered using integrative vectors and the auxotrophic mutant of BCG complemented with a plasmid carrying a wild-type complementing gene. In this study, we have constructed an integrative E. coli-mycobacterial shuttle plasmid, p2auxo.HIVA(int), expressing the HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism for plasmid selection and maintenance...
April 20, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28425576/bone-marrow-adipose-and-lung-tissue-derived-murine-mesenchymal-stromal-cells-release-different-mediators-and-differentially-affect-airway-and-lung-parenchyma-in-experimental-asthma
#7
Soraia C Abreu, Mariana A Antunes, Debora G Xisto, Fernanda F Cruz, Vivian C Branco, Elga Bandeira, Jamil Zola Kitoko, Almair F de Araújo, Ludmilla Dellatorre-Texeira, Priscilla C Olsen, Daniel J Weiss, Bruno L Diaz, Marcelo M Morales, Patricia R M Rocco
Mesenchymal stromal cells (MSCs) from different sources have differential effects on lung injury. To compare the effects of murine MSCs from bone marrow (BM), adipose tissue (AD), and lung tissue (LUNG) on inflammatory and remodeling processes in experimental allergic asthma, female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) or saline (C). Twenty-four hours after the last challenge, mice received either saline (50 µl, SAL), BM-MSCs, AD-MSCs, or LUNG-MSCs (10(5) cells per mouse in 50 µl total volume) intratracheally...
April 20, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28425451/ifn%C3%AE-protects-neurons-from-damage-in-a-murine-model-of-hiv-1-associated-brain-injury
#8
Victoria E Thaney, Alan M O'Neill, Melanie M Hoefer, Ricky Maung, Ana B Sanchez, Marcus Kaul
Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424686/mucosal-and-systemic-immune-responses-to-influenza-h7n9-antigen-ha1-2-co-delivered-intranasally-with-flagellin-or-polyethyleneimine-in-mice-and-chickens
#9
Li Song, Dan Xiong, Hongqin Song, Lili Wu, Meihua Zhang, Xilong Kang, Zhiming Pan, Xinan Jiao
Consecutive cases of human infection with H7N9 influenza viruses since 2013 in China have prompted efforts to develop an effective treatment. Subunit vaccines introduced by intranasal administration can block an infection at its primary site; flagellin (fliC) and polyethyleneimine (PEI) have been shown to be potent adjuvants. We previously generated the hemagglutinin (HA)1-2-fliC fusion protein consisting of the globular head domain (HA1-2; amino acids 62-284) of HA fused with Salmonella typhimurium fliC. In the present study, we investigated its effectiveness of both flagellin and PEI as mucosal adjuvants for the H7N9 influenza subunit vaccine...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28424682/interactions-between-type-1-interferons-and-the-th17-response-in-tuberculosis-lessons-learned-from-autoimmune-diseases
#10
REVIEW
Bas C Mourik, Erik Lubberts, Jurriaan E M de Steenwinkel, Tom H M Ottenhoff, Pieter J M Leenen
The classical paradigm of tuberculosis (TB) immunity, with a central protective role for Th1 responses and IFN-γ-stimulated cellular responses, has been challenged by unsatisfactory results of vaccine strategies aimed at enhancing Th1 immunity. Moreover, preclinical TB models have shown that increasing IFN-γ responses in the lungs is more damaging to the host than to the pathogen. Type 1 interferon signaling and altered Th17 responses have also been associated with active TB, but their functional roles in TB pathogenesis remain to be established...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28424064/effectiveness-of-triple-therapy-with-direct-acting-antivirals-for-hepatitis-c-genotype-1-infection-application-of-propensity-score-matching-in-a-national-hcv-treatment-registry
#11
Emma Gray, David J Pasta, Suzanne Norris, Aisling O'Leary
BACKGROUND: Observational studies are used to measure the effectiveness of an intervention in non-experimental, real world scenarios at the population level and are recognised as an important component of the evidence pyramid. Such data can be accrued through prospective cohort studies and a patient registry is a proven method for this type of study. The national hepatitis C (HCV) registry was established in Ireland in 2012 with the aim of monitoring the clinical and economic outcomes from new, high cost regimens for the treatment of HCV infection...
April 19, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28419615/involvement-of-herpes-simplex-virus-type-1-ul13-protein-kinase-in-the-induction-of-socs-genes-the-negative-regulator-of-cytokine-signaling
#12
Yuka Sato, Tetsuo Koshizuka, Kei Ishibashi, Koichi Hashimoto, Ken Ishioka, Kazufumi Ikuta, Shin-Ichi Yokota, Nobuhiro Fujii, Tatsuo Suzutani
The suppressor of cytokine signaling (SOCS) family consists of 8 members and suppresses various cytokine signaling pathways including interferon (IFN) signaling. Therefore, some viruses have evolved molecular mechanisms to induce SOCS proteins in order to escape from host immunity. Herpes simplex virus type 1 (HSV-1) has a mechanism for escaping from type I IFN by induction of SOCS1 and SOCS3 as well. In this study, expression of 8 members of the SOCS family by HSV-1 infection was comparatively analyzed by quantitative reverse transcription PCR...
April 17, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28419140/niche-matters-the-comparison-between-bone-marrow-stem-cells-and-endometrial-stem-cells-and-stromal-fibroblasts-reveal-distinct-migration-and-cytokine-profiles-in-response-to-inflammatory-stimulus
#13
Masuma Khatun, Anna Sorjamaa, Marika Kangasniemi, Meeri Sutinen, Tuula Salo, Annikki Liakka, Petri Lehenkari, Juha S Tapanainen, Olli Vuolteenaho, Joseph C Chen, Siri Lehtonen, Terhi T Piltonen
OBJECTIVE: Intrinsic inflammatory characteristics play a pivotal role in stem cell recruitment and homing through migration where the subsequent change in niche has been shown to alter these characteristics. The bone marrow mesenchymal stem cells (bmMSCs) have been demonstrated to migrate to the endometrium contributing to the stem cell reservoir and regeneration of endometrial tissue. Thus, the aim of the present study was to compare the inflammation-driven migration and cytokine secretion profile of human bmMSCs to endometrial mesenchymal stem cells (eMSCs) and endometrial fibroblasts (eSFs)...
2017: PloS One
https://www.readbyqxmd.com/read/28417642/equilibrative-nucleoside-transporter-1-expression-in-primary-human-hepatocytes-is-highly-variable-and-determines-uptake-of-ribavirin
#14
Kanwal Baloch, Liqiong Chen, Ameer A Memon, Laura Dexter, William Irving, Mohammad Ilyas, Brian J Thomson
Aims Ribavirin is a nucleoside analogue and remains a necessary component of both interferon-based and directly acting anti-viral regimens for the treatment of hepatitis C virus infection. The achievable concentration of ribavirin within hepatocytes is likely to be an important determinant of therapeutic outcome. In vitro expression levels of equilibrative nucleoside transporter 1 (ENT1) has been shown to be a predictor of treatment response in patients receiving nucleoside-based chemotherapeutic agents. We therefore investigated whether a similar relationship existed between ENT1 expression and ribavirin uptake in freshly isolated primary hepatocytes...
April 2017: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/28413316/ginsenoside-rc-from-panax-ginseng-exerts-anti-inflammatory-activity-by-targeting-tank-binding-kinase-1-interferon-regulatory-factor-3-and-p38-atf-2
#15
Tao Yu, Yanyan Yang, Yi-Seong Kwak, Gwan Gyu Song, Mi-Yeon Kim, Man Hee Rhee, Jae Youl Cho
BACKGROUND: Ginsenoside Rc (G-Rc) is one of the major protopanaxadiol-type saponins isolated from Panax ginseng, a well-known medicinal herb with many beneficial properties including anticancer, anti-inflammatory, antiobesity, and antidiabetic effects. In this study, we investigated the effects of G-Rc on inflammatory responses in vitro and examined the mechanisms of these effects. METHODS: The in vitro inflammation system used lipopolysaccharide-treated macrophages, tumor necrosis factor-α/interferon-γ-treated synovial cells, and HEK293 cells transfected with various inducers of inflammation...
April 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28413215/successful-withdrawal-of-insulin-therapy-after-post-treatment-clearance-of-hepatitis-c-virus-in-a-man-with-type-2-diabetes
#16
Timothy M E Davis, Wendy A Davis, Gary Jeffrey
BACKGROUND Chronic hepatitis C virus (HCV) infection is associated with increased insulin resistance and risk of type 2 diabetes. Successful antiviral treatment can improve insulin resistance and allow a reduction in blood glucose-lowering treatment. There have been case reports of a reduced insulin requirement in this situation, although 1 case in which insulin was stopped exhibited a subsequent deterioration in glycemic control. CASE REPORT A 55-year-old Italian man was diagnosed with HCV infection in 2000 at the age of 39 years and with type 2 diabetes 6 years later...
April 17, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28412968/interleukin-1-primes-human-mesenchymal-stem-cells-towards-an-anti-inflammatory-and-pro-trophic-phenotype-in-vitro
#17
Elena Redondo-Castro, Catriona Cunningham, Jonjo Miller, Licia Martuscelli, Sarah Aoulad-Ali, Nancy J Rothwell, Cay M Kielty, Stuart M Allan, Emmanuel Pinteaux
BACKGROUND: Inflammation is a key contributor to central nervous system (CNS) injury such as stroke, and is a major target for therapeutic intervention. Effective treatments for CNS injuries are limited and applicable to only a minority of patients. Stem cell-based therapies are increasingly considered for the treatment of CNS disease, because they can be used as in-situ regulators of inflammation, and improve tissue repair and recovery. One promising option is the use of bone marrow-derived mesenchymal stem cells (MSCs), which can secrete anti-inflammatory and trophic factors, can migrate towards inflamed and injured sites or can be implanted locally...
April 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28412547/intracellular-dna-sensing-pathway-of-cgas-cgamp-is-decreased-in-human-newborns-and-young-children
#18
Zhan-Sheng Wang, Yu-Lu Liu, Nan Mi, Dao-Yun Duan
Newborns are highly susceptible to DNA virus infections, which may result from the characteristics of neonatal innate immune systems. Here we analyzed for the first time the development of innate immune sensing and signaling of intracellular DNA virus infection in human newborns and young children. Both mRNA and protein expression of cGAS, an intracellular DNA sensor, were shown to be significantly reduced in neonatal peripheral blood mononuclear cells (PBMCs). In addition, cGAS expression in neonatal PBMCs could be induced upon herpes simplex virus type 1 (HSV-1) or interferon-α (IFNα) stimulation...
April 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28411684/in-vivo-antimalarial-activity-of-synthetic-hepcidin-against-plasmodium-berghei-in-mice
#19
Ya-Qun Fang, Chuan-Bin Shen, Ning Luan, Hui-Min Yao, Chen-Bo Long, Ren Lai, Xiu-Wen Yan
The present study was designed to investigate the antimalarial activity of synthetic hepcidin and its effect on cytokine secretion in mice infected with Plasmodium berghei. The mice were infected with P. berghei intravenously and treated with hepcidin according to 4-day suppression test and Rane's test. The serum levels of interleukins (IL-1β, IL-2, IL-6, IL-10, IL-12p70, and IL-17A), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the experimental mice were determined using a cytometric bead array (CBA) kit...
March 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28411130/ifitm1-suppression-blocks-proliferation-and-invasion-of-aromatase-inhibitor-resistant-breast-cancer-in%C3%A2-vivo-by-jak-stat-mediated-induction-of-p21
#20
Asona J Lui, Eric S Geanes, Joshua Ogony, Fariba Behbod, Jordan Marquess, Kelli Valdez, William Jewell, Ossama Tawfik, Joan Lewis-Wambi
Interferon induced transmembrane protein 1 (IFITM1) belongs to a family of interferon stimulated genes (ISGs) that is associated with tumor progression and DNA damage resistance, however, its role in endocrine resistance is not known. Here, we correlate IFITM1 expression with clinical stage and poor response to endocrine therapy in a tissue microarray consisting of 94 estrogen receptor (ER)-positive breast tumors. IFITM1 overexpression is confirmed in the AI-resistant MCF-7:5C cell line and not found in AI-sensitive MCF-7 cells...
April 12, 2017: Cancer Letters
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