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https://www.readbyqxmd.com/read/27907183/activation-of-innate-and-adaptive-immunity-by-a-recombinant-human-cytomegalovirus-strain-expressing-an-nkg2d-ligand
#1
Adriana Tomić, Pavankumar R Varanasi, Mijo Golemac, Suzana Malić, Peggy Riese, Eva M Borst, Eva Mischak-Weissinger, Carlos A Guzmán, Astrid Krmpotić, Stipan Jonjić, Martin Messerle
Development of an effective vaccine against human cytomegalovirus (HCMV) is a need of utmost medical importance. Generally, it is believed that a live attenuated vaccine would best provide protective immunity against this tenacious pathogen. Here, we propose a strategy for an HCMV vaccine that aims at the simultaneous activation of innate and adaptive immune responses. An HCMV strain expressing the host ligand ULBP2 for the NKG2D receptor was found to be susceptible to control by natural killer (NK) cells, and preserved the ability to stimulate HCMV-specific T cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27907087/prenylated-polyphenols-from-clusiaceae-and-calophyllaceae-with-immunomodulatory-activity-on-endothelial-cells
#2
Caroline Rouger, Sylvain Pagie, Séverine Derbré, Anne-Marie Le Ray, Pascal Richomme, Béatrice Charreau
Endothelial cells (ECs) are key players in inflammation and immune responses involved in numerous pathologies. Although attempts were experimentally undertaken to prevent and control EC activation, drug leads and probes still remain necessary. Natural products (NPs) from Clusiaceous and Calophyllaceous plants were previously reported as potential candidates to prevent endothelial dysfunction. The present study aimed to identify more precisely the molecular scaffolds that could limit EC activation. Here, 13 polyphenols belonging to 5 different chemical types of secondary metabolites (i...
2016: PloS One
https://www.readbyqxmd.com/read/27903740/protective-t-cell-responses-featured-by-concordant-recognition-of-middle-east-respiratory-syndrome-coronavirus-derived-cd8-t-cell-epitopes-and-host-mhc
#3
William J Liu, Jiaming Lan, Kefang Liu, Yao Deng, Yanfeng Yao, Shaolian Wu, Hong Chen, Lingling Bao, Haifeng Zhang, Min Zhao, Qihui Wang, Lingxia Han, Yan Chai, Jianxun Qi, Jincun Zhao, Songdong Meng, Chuan Qin, George F Gao, Wenjie Tan
The coordinated recognition of virus-derived T cell epitopes and MHC molecules by T cells plays a pivotal role in cellular immunity-mediated virus clearance. It has been demonstrated that the conformation of MHC class I (MHC I) molecules can be adjusted by the presented peptide, which impacts T cell activation. However, it is still largely unknown whether the conformational shift of MHC I influences the protective effect of virus-specific T cells. In this study, utilizing the Middle East respiratory syndrome coronavirus-infected mouse model, we observed that through the unusual secondary anchor Ile5, a CD8(+) T cell epitope drove the conformational fit of Trp(73) on the α1 helix of murine MHC I H-2K(d) In vitro renaturation and circular dichroism assays indicated that this shift of the structure did not influence the peptide/MHC I binding affinity...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27901642/a-generic-rna-pulsed-dc-based-approach-for-developing-therapeutic-intervention-against-nasopharyngeal-carcinoma
#4
Rajeev K Tyagi, Rajesh Parmar, Naisargee Patel
The recurrent nasopharyngeal carcinoma of head-and-neck cancers pathology showed unique symptoms and clinical characteristics. The complexity of pathology poses challenges for developing therapeutic interventional approaches against nasopharyngeal carcinoma (NPC). The conventional treatment regimens offer limited local control and survival, which, leads to adverse delayed complications. Our study present a generic monocyte derived dendritic cell (MoDC) vaccine strategy for NPC in which RNA is used as a source of tumor-associated antigens (TAAgs)...
November 30, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27895620/excessive-cytosolic-dna-fragments-as-a-potential-trigger-of-graves-disease-an-encrypted-message-sent-by-animal-models
#5
REVIEW
Yuqian Luo, Aya Yoshihara, Kenzaburo Oda, Yuko Ishido, Koichi Suzuki
Graves' hyperthyroidism is caused by autoantibodies directed against the thyroid-stimulating hormone receptor (TSHR) that mimic the action of TSH. The establishment of Graves' hyperthyroidism in experimental animals has proven to be an important approach to dissect the mechanisms of self-tolerance breakdown that lead to the production of thyroid-stimulating TSHR autoantibodies (TSAbs). "Shimojo's model" was the first successful Graves' animal model, wherein immunization with fibroblasts cells expressing TSHR and a major histocompatibility complex (MHC) class II molecule, but not either alone, induced TSAb production in AKR/N (H-2(k)) mice...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27893611/absence-of-mir-182-augments-cardiac-allograft-survival
#6
Liang Wei, Vandana Kaul, Xiumei Qu, Xiaoxing Xiong, Audrey H Lau, Naoharu Iwai, Olivia M Martinez, Sheri M Krams
BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate the posttranscriptional expression of target genes and are important regulators in immune responses. Previous studies demonstrated that the miRNA, miR-182 was significantly increased during allograft rejection. Further, the transcription factor Forkhead box (FOX) protein 1, (FOXO1) was shown to be a target of miR-182. The aim of this study is to further examine the role of miR-182 in alloimmune responses. METHODS: Transplantation of BALB/c cardiac allografts was performed in C57BL/6, miR-182, B6...
November 23, 2016: Transplantation
https://www.readbyqxmd.com/read/27891500/interspecies-communication-between-pathogens-and-immune-cells-via-bacterial-membrane-vesicles
#7
Katerina S Jurkoshek, Ying Wang, Jaffre J Athman, Marian R Barton, Pamela A Wearsch
The production of extracellular vesicles is a universal mechanism for intercellular communication that is conserved across kingdoms. Prokaryotes secrete 50-250 nm membrane vesicles (MVs) in a manner that is regulated by environmental stress and is thought to promote survival. Since many types of host-derived stress are encountered during infection, this implies an important role for MV secretion in bacterial pathogenesis. Accordingly, MVs produced by gram-positive and gram-negative pathogens contain toxins, virulence factors, and other molecules that promote survival in the host...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27891225/unraveling-the-role-of-preexisting-immunity-in-prostate-cancer-patients-vaccinated-with-a-her-2-neu-hybrid-peptide
#8
Ioannis F Voutsas, Eleftheria A Anastasopoulou, Panagiotis Tzonis, Michael Papamichail, Sonia A Perez, Constantin N Baxevanis
BACKGROUND: Cancer vaccines aim at eliciting not only an immune response against specific tumor antigens, but also at enhancing a preexisting immunity against the tumor. In this context, we recently reported on the levels of preexisting immunity in prostate cancer patients vaccinated with the HER-2 hybrid peptide (AE37), during a phase I clinical trial. The purpose of the current study was to correlate between preexisting immunity to the native HER-2 peptide, AE36, and expression of HLA-A2 and -A24 molecules with the clinical outcome...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27874963/study-on-the-functions-and-mechanism-of-immune-functions-of-human-telomerase-reverse-transcriptase-regulating-dendritic-cells-treating-sepsis
#9
H-M Chen, L-Q Wang, H-P Wan, H-Z Wei, L-C Ke, C-Y Liu, Q-Y Tan
OBJECTIVE: We analyzed the functions and mechanisms of immune functions of human telomerase reverse transcriptase regulating dendritic cells (DC) treating sepsis of mice models. MATERIALS AND METHODS: Eighty clean grade Balb/c animals aged from 6 to 8 weeks, weighted from 18 g to 22 g were selected for this study. The DC cells were harvested from the animals and cultivated to transfect with the recombinant eukaryotic expression plasmid hTERT-IRES2-EGFP construct...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27874054/combinational-immunotherapy-with-allo-dribble-vaccines-and-anti-ox40-co-stimulation-leads-to-generation-of-cross-reactive-effector-t-cells-and-tumor-regression
#10
Guangjie Yu, Yuhuan Li, Zhihua Cui, Nicholas P Morris, Andrew D Weinberg, Bernard A Fox, Walter J Urba, Lixin Wang, Hong-Ming Hu
It is well-known that vaccines comprising of irradiated whole tumor cells or tumor-derived heat shock proteins can generate tumor-specific immune responses. In contrast, we showed recently that vaccines composed of autophagosomes (DRibbles) derived from syngeneic sarcomas could induce cross-reactive T-cell responses and cross-protection against the tumor. This unusual property of DRibbles was related to the selective recruitment of defective ribosomal products (DRiPs) and other short-lived proteins (SLiPs) into autophagosomes via sequestosome (SQSTM1, p62) mediated association of ubiquitinated SLiPs to the autophagy gene product LC3...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872213/autocrine-type-i-ifn-signaling-in-dendritic-cells-stimulated-with-fungal-%C3%AE-glucans-or-lipopolysaccharide-promotes-cd8-t-cell-activation
#11
Nargess Hassanzadeh-Kiabi, Alberto Yáñez, Ivy Dang, Gislâine A Martins, David M Underhill, Helen S Goodridge
Type I IFNs are key mediators of immune defense against viruses and bacteria. Type I IFNs were also previously implicated in protection against fungal infection, but their roles in antifungal immunity have not been thoroughly investigated. A recent study demonstrated that bacterial and fungal β-glucans stimulate IFN-β production by dendritic cells (DCs) following detection by the Dectin-1 receptor, but the effects of β-glucan-induced type I IFNs have not been defined. We investigated whether type I IFNs regulate CD8 T cell activation by fungal β-glucan particle-stimulated DCs...
November 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27863400/differentiated-regulation-of-immune-response-related-genes-between-luad-and-lusc-subtypes-of-lung-cancers
#12
Mengzhu Chen, Xiuying Liu, Jie Du, Xiu-Jie Wang, Lixin Xia
Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the two major subtypes of lung cancer, with LUSC exhibits faster progression rate than LUAD. To investigate the roles of immune-response related genes (IRGs) in lung cancer progression, we used LUAD and LUSC samples at different cancer progression stages, and identified that the expression profiles of IRGs could serve as a better classification marker for cancerous tissues of both LUAD and LUSC. We found that the expression changes of IRGs were different between LUAD and LUSC...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27863161/hla-dr-polymorphisms-influence-in-vivo-responses-to-staphylococcal-toxic-shock-syndrome-toxin-1-in-a-transgenic-mouse-model
#13
A Krogman, A Tilahun, C S David, V R Chowdhary, M P Alexander, G Rajagopalan
Toxic shock syndrome toxin-1 (TSST-1) is a potent superantigen produced by Staphylococcus aureus. In addition to menstrual and nonmenstrual toxic shock syndromes, TSST-1 is also implicated in the immunopathogenesis of pneumonia, infective endocarditis, neonatal exanthematous disease, and atopic dermatitis among others. Superantigens first bind to major histocompatibility complex (MHC) class II molecules and then activate a large proportion of T cells by cross-linking their T cell receptor. As binding to MHC class II molecules is a critical step in the robust activation of the immune system by TSST-1 and other superantigens, polymorphic variations between different HLA-DR alleles could potentially influence the magnitude of immune activation and immunopathology caused by TSST-1...
November 15, 2016: HLA
https://www.readbyqxmd.com/read/27861821/effects-of-c2ta-genetic-polymorphisms-on-mhc-class-ii-expression-and-autoimmune-diseases
#14
Anthony Cy Yau, Fredrik Piehl, Tomas Olsson, Rikard Holmdahl
Antigen presentation by the major histocompatibility complex class II (MHC-II) to CD4(+) T cells is important in adaptive immune responses. The class II transactivator (CIITA in human and C2TA in mouse) is the master regulator of MHC-II gene expression. It coordinates the transcription factors necessary for the transcription of MHC-II molecules. In humans, genetic variation in C2ta has been associated with differential expression of MHC-II and susceptibility to autoimmune diseases. Here we made use of a C2ta congenic mouse strain (expressing MHC-II haplotype H-2(q) ) to investigate the effect of the natural genetic polymorphisms in type I promoter of C2ta on MHC-II expression and function...
November 15, 2016: Immunology
https://www.readbyqxmd.com/read/27861124/rab22a-controls-mhc-i-intracellular-trafficking-and-antigen-cross-presentation-by-dendritic-cells
#15
Ignacio Cebrian, Cristina Croce, Néstor A Guerrero, Nicolas Blanchard, Luis S Mayorga
Cross-presentation by MHC class I molecules allows the detection of exogenous antigens by CD8(+) T lymphocytes. This process is crucial to initiate cytotoxic immune responses against many pathogens (i.e., Toxoplasma gondii) and tumors. To achieve efficient cross-presentation, dendritic cells (DCs) have specialized endocytic pathways; however, the molecular effectors involved are poorly understood. In this work, we identify the small GTPase Rab22a as a key regulator of MHC-I trafficking and antigen cross-presentation by DCs...
December 2016: EMBO Reports
https://www.readbyqxmd.com/read/27859042/hla-g-promotes-myeloid-derived-suppressor-cell-mdsc-accumulation-and-suppressive-activity-during-human-pregnancy-through-engagement-of-the-receptor-ilt4
#16
Natascha Köstlin, Anna-Lena Ostermeir, Bärbel Spring, Julian Schwarz, Alexander Marmé, Christina B Walter, Christian F Poets, Christian Gille
Establishing and maintaining maternal-fetal tolerance is essential for a successful pregnancy; failure of immunological adaptation to pregnancy leads to severe complications such as abortion or preterm delivery. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that suppress T-cell responses, expand during pregnancy and thus may play a role in tolerance induction. Human leucocyte antigen G (HLA-G) is a major histocompatibility complex (MHC) I molecule with immune-modulatory properties, which is expressed during pregnancy...
November 10, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27837111/age-associated-b-cells-with-proinflammatory-characteristics-are-expanded-in-a-proportion-of-multiple-sclerosis-patients
#17
Nele Claes, Judith Fraussen, Marjan Vanheusden, Niels Hellings, Piet Stinissen, Bart Van Wijmeersch, Raymond Hupperts, Veerle Somers
Immune aging occurs in the elderly and in autoimmune diseases. Recently, IgD(-)CD27(-) (double negative, DN) and CD21(-)CD11c(+) (CD21(low)) B cells were described as age-associated B cells with proinflammatory characteristics. This study investigated the prevalence and functional characteristics of DN and CD21(low) B cells in multiple sclerosis (MS) patients. Using flow cytometry, we demonstrated a higher proportion of MS patients younger than 60 y with peripheral expansions of DN (8/41) and CD21(low) (9/41) B cells compared with age-matched healthy donors (1/33 and 2/33, respectively), which indicates an increase in age-associated B cells in MS patients...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27835636/in-vitro-evaluation-of-the-biological-responses-of-canine-macrophages-challenged-with-plga-nanoparticles-containing-monophosphoryl-lipid-a
#18
Delphine Guldner, Julianne K Hwang, Maria Clara D Cardieri, Meaghan Eren, Parissa Ziaei, M Grant Norton, Cleverson D Souza
Poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) have been considerably studied as a promising biodegradable delivery system to induce effective immune responses and to improve stability, safety, and cost effectiveness of vaccines. The study aimed at evaluating early inflammatory effects and cellular safety of PLGA NPs, co-encapsulating ovalbumin (PLGA/OVA NPs), as a model antigen and the adjuvant monophosphoryl lipid A (PLGA/MPLA NPs) as an adjuvant, on primary canine macrophages. The PLGA NPs constructs were prepared following the emulsion-solvent evaporation technique and further physic-chemically characterized...
2016: PloS One
https://www.readbyqxmd.com/read/27835581/regulatory-landscape-and-clinical-implication-of-mbd3-in-human-malignant-glioma
#19
Yi Cui, Jian Li, Ling Weng, Sara E Wirbisky, Jennifer L Freeman, Jingping Liu, Qing Liu, Xianrui Yuan, Joseph Irudayaraj
In this article we inspect the roles and functions of the methyl-CpG-binding domain protein 3 (MBD3) in human malignant glioma, to assess its potential as an epigenetic biomarker for prognosis. The regulatory effects of MBD3 on glioma transcriptome were first profiled by high-throughput microarray. Our results indicate that MBD3 is involved in both transcriptional activation and repression. Furthermore, MBD3 fine-controls a spectrum of proteins critical for cellular metabolism and proliferation, thereby contributing to an exquisite anti-glioma network...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27832583/salmonella-gives-march-ing-orders-to-mhc-ii
#20
Patrick A McLaughlin, Adrianus W M van der Velden
How bacterial pathogens evade adaptive immunity is not well understood. In this issue of Cell Host & Microbe, Bayer-Santos et al. (2016) show that the Salmonella effector protein SteD mediates MARCH8-dependent ubiquitination of class II MHC molecules, thereby inhibiting antigen presentation and limiting T cell responses.
November 9, 2016: Cell Host & Microbe
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