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https://www.readbyqxmd.com/read/28546072/dendrimer-conjugated-peptide-vaccine-enhances-clearance-of-chlamydia-trachomatis-genital-infection
#1
Ingrid S Ganda, Qian Zhong, Mirabela Hali, Ricardo L C Albuquerque, Francine F Padilha, Sandro R P da Rocha, Judith A Whittum-Hudson
Peptide-based vaccines have emerged in recent years as promising candidates in the prevention of infectious diseases. However, there are many challenges to maintaining in vivo peptide stability and enhancement of peptide immunogenicity to generate protective immunity which enhances clearance of infections. Here, a dendrimer-based carrier system is proposed for peptide-based vaccine delivery, and shows its anti-microbial feasibility in a mouse model of Chlamydia trachomatis. Chlamydiae are the most prevalent sexually transmitted bacteria worldwide, and also the causal agent of trachoma, the leading cause of preventable infectious blindness...
May 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28545552/hrhpv-e5-oncoprotein-immune-evasion-and-related-immunotherapies
#2
REVIEW
Antonio Carlos de Freitas, Talita Helena Araújo de Oliveira, Marconi Rego Barros, Aldo Venuti
The immune response is a key factor in the fight against HPV infection and related cancers, and thus, HPV is able to promote immune evasion through the expression of oncogenes. In particular, the E5 oncogene is responsible for modulation of several immune mechanisms, including antigen presentation and inflammatory pathways. Moreover, E5 was suggested as a promising therapeutic target, since there is still no effective medical therapy for the treatment of HPV-related pre-neoplasia and cancer. Indeed, several studies have shown good prospective for E5 immunotherapy, suggesting that it could be applied for the treatment of pre-cancerous lesions...
May 25, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28544973/pegylation-of-a-tlr2-agonist-based-vaccine-delivery-system-improves-antigen-trafficking-and-the-magnitude-of-ensuing-antibody-and-cd8-t-cell-responses
#3
Toshiki Sekiya, Junya Yamagishi, John Henry V Gray, Paul G Whitney, Axel Martinelli, Weiguang Zeng, Chinn Yi Wong, Chihiro Sugimoto, David C Jackson, Brendon Y Chua
The lipopeptide R4Pam2Cys is an agonist for toll-like receptor-2 (TLR2), a key pathogen-associated molecular pattern receptor expressed on many antigen-presenting cells such as dendritic cells (DCs). Electrostatic association of R4Pam2Cys with soluble protein antigens significantly enhances their immunogenicity and there is evidence to suggest that reducing the size of suitably adjuvanted-antigen complexes in solution may further improve their immunostimulatory capabilities. In this study, we investigated how incorporation of polyethylene glycol (PEG) into R4Pam2Cys affects the size, activity and efficacy of formed antigen-lipopeptide complexes...
May 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28544329/dissolving-microneedle-arrays-for-transdermal-delivery-of-amphiphilic-vaccines
#4
Myunggi An, Haipeng Liu
Amphiphilic vaccine based on lipid-polymer conjugates is a new type of vaccine capable of self-delivering to the immune system. When injected subcutaneously, amphiphilic vaccines efficiently target antigen presenting cells in the lymph nodes (LNs) via a unique albumin-mediated transport and uptake mechanism and induce potent humoral and cellular immune responses. However, whether this new type of vaccine can be administrated via a safe, convenient microneedle-based transdermal approach remains unstudied. For such skin barrier-disruption systems, a simple application of microneedle arrays (MNs) is desired to disrupt the stratum corneum, and for rapid and pain-free self-administration of vaccines into the skin, the anatomic place permeates with an intricate mesh of lymphatic vessels draining to LNs...
May 19, 2017: Small
https://www.readbyqxmd.com/read/28543878/mitap-compliant-characterisation-of-human-regulatory-macrophages
#5
REVIEW
James A Hutchinson, Nobert Ahrens, Edward K Geissler
This article provides a transparent description of Mreg_UKR cell products, including manufacture and quality-control processes, using the structure and vocabulary of the 'Minimum Information about Tolerogenic Antigen-presenting Cells' reporting guidelines. This information is intended as a resource for those in the field, as well as a stimulus to develop a new wave of immunoregulatory and tissue-reparative monocyte-derived cell therapies. This article is protected by copyright. All rights reserved.
May 20, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28542929/the-immune-response-to-prevotella-bacteria-in-chronic-inflammatory-disease
#6
REVIEW
Jeppe Madura Larsen
The microbiota plays a central role in human health and disease by shaping immune development, immune responses, metabolism, and protecting from invading pathogens. Technical advances that allow comprehensive characterization of microbial communities by genetic sequencing have sparked the hunt for disease modulating bacteria. Emerging studies in humans have linked increased abundance of Prevotella species at mucosal sites to localized and systemic disease, including periodontitis, bacterial vaginosis, rheumatoid arthritis, metabolic disorders, and low-grade systemic inflammation...
May 19, 2017: Immunology
https://www.readbyqxmd.com/read/28542586/antigen-delivery-to-dendritic-cells-shapes-human-cd4-and-cd8-t-cell-memory-responses-to-staphylococcus-aureus
#7
Julia Uebele, Christoph Stein, Minh-Thu Nguyen, Anja Schneider, Franziska Kleinert, Olga Tichá, Gabriele Bierbaum, Friedrich Götz, Isabelle Bekeredjian-Ding
Intracellular persistence of Staphylococcus aureus favors bacterial spread and chronic infections. Here, we provide evidence for the existence of human CD4+ and CD8+ T cell memory against staphylococcal antigens. Notably, the latter could provide a missing link in our understanding of immune control of intracellular S. aureus. The analyses showed that pulsing of monocyte-derived dendritic cells (MoDC) with native staphylococcal protein antigens induced release of Th2-associated cytokines and mediators linked to T regulatory cell development (G-CSF, IL-2 and IL-10) from both CD4+ and CD8+ T cells, thus revealing a state of tolerance predominantly arising from preformed memory T cells...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28541408/loss-of-homeostatic-microglia-and-patterns-of-their-activation-in-active-multiple-sclerosis
#8
Tobias Zrzavy, Simon Hametner, Isabella Wimmer, Oleg Butovsky, Howard L Weiner, Hans Lassmann
Microglia and macrophages accumulate at the sites of active demyelination and neurodegeneration in the multiple sclerosis brain and are thought to play a central role in the disease process. We used recently described markers to characterize the origin and functional states of microglia/macrophages in acute, relapsing and progressive multiple sclerosis. We found microglia activation in normal white matter of controls and that the degree of activation increased with age. This microglia activation was more pronounced in the normal-appearing white matter of patients in comparison to controls and increased with disease duration...
May 24, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28541089/decreased-frequency-of-peripheral-blood-cd8-cd25-foxp3-regulatory-t-cells-correlates-with-il-33-levels-in-pre-eclampsia
#9
Jianxiu Yu, Lei Qian, Fenghui Wu, Ming Li, Wei Chen, Hongyou Wang
OBJECTIVE: We aimed to investigate the role of CD8(+)CD25(+)Foxp3(+)regulatory T (Treg) cells in pre-eclampsia (PE). METHODS: This was a cross-sectional study of 46 patients with PE and 24 normotensive women within the third trimester of gestation. We analyzed the percentages of CD8(+)CD25(+)Foxp3(+)Treg cells in peripheral blood using flow cytometry and the serum levels of interleukin (IL)-6, IL-17A, IL-10, TGF-β1, IL-1β, and IL-33 by Luminex 200. RESULTS: We found that patients with PE had lower percentages of CD8(+)CD25(+)Foxp3(+)Treg cells than normotensive pregnant women...
May 25, 2017: Hypertension in Pregnancy
https://www.readbyqxmd.com/read/28540936/antigen-presenting-cell-targeted-lentiviral-vectors-do-not-support-the-development-of-productive-t-cell-effector-responses-implications-for-in-vivo-targeted-vaccine-delivery
#10
C Goyvaerts, Y De Vlaeminck, D Escors, S Lienenklaus, M Keyaerts, G Raes, K Breckpot
Targeting transgene expression specifically to antigen-presenting cells (APCs) has been put forward as a promising strategy to direct the immune system towards immunity. We developed the nanobody-display technology to restrict the tropism of lentiviral vectors (LVs) to APCs. However, we observed that immunization with APC-targeted LVs (DC2.1-LVs) did not evoke strong antigen-specific T-cell immunity when compared to immunization with broad tropism LVs (VSV.G-LVs). In this study, we report that VSV.G-LVs are more immunogenic than DC2...
May 25, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28539453/epigenetic-metabolite-acetate-inhibits-class-i-ii-histone-deacetylases-promotes-histone-acetylation-and-increases-hiv-1-integration-in-cd4-t-cells
#11
Jean-François Bolduc, Laurent Hany, Corinne Barat, Michel Ouellet, Michel J Tremblay
In this study, we investigated the effect of acetate, the most concentrated short-chain fatty acid (SCFA) in the gut and bloodstream, on the susceptibility of primary human CD4(+) T cells to HIV-1 infection. We report that HIV-1 replication is increased in CD3/CD28-costimulated CD4(+) T cells upon acetate treatment. This enhancing effect correlates with an increased expression of the early activation marker CD69 and impaired class I/II histone deacetylase (HDAC) activity. In addition, acetate enhances acetylation of histones H3 and H4 and augments HIV-1 integration in the genome of CD4(+) T cells...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539278/-construction-of-specific-artificial-antigen-presenting-cells-for-in-vitro-activation-of-cd19-chimeric-antigen-receptor-t-cells
#12
Yao-Jun Peng, Qi-Yan Wu, Hong-Yu Liu, Jian Zhao, Hua-Feng Wei
OBJECTIVE: To construct CD19-specific artificial antigen-presenting cells (aAPCs) for in vitro activation and expansion of CD19 chimeric antigen receptor (CAR)-modified T cells (CD19-CAR-T) and investigate their cytotoxic effect. METHODS: CD19-specific aAPCs (NIH3T3-CD19/86, NIH3T3-CD19/86/137L) expressing costimulatory molecules CD86 and/or CD137L were prepared on the basis of NIH3T3 backbone cells by lentivirus-mediated gene transfer. Irradiated CD19-specific aAPCs were co-cultured with CD19-CAR-T cells to activate and amplify CD19-CAR-T cells...
May 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#13
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537251/antigen-specific-cd8-t-cell-feedback-activates-nlrp3-inflammasome-in-antigen-presenting-cells-through-perforin
#14
Yikun Yao, Siyuan Chen, Mengtao Cao, Xing Fan, Tao Yang, Yin Huang, Xinyang Song, Yongqin Li, Lilin Ye, Nan Shen, Yufang Shi, Xiaoxia Li, Feng Wang, Youcun Qian
The connection between innate and adaptive immunity is best exemplified by antigen presentation. Although antigen-presenting cells (APCs) are required for antigen receptor-mediated T-cell activation, how T-cells feedback to APCs to sustain an antigen-specific immune response is not completely clear. Here we show that CD8(+) T-cell (also called cytotoxic T lymphocytes, CTL) feedback activates the NLRP3 inflammasome in APCs in an antigen-dependent manner to promote IL-1β maturation. Perforin from antigen-specific CTLs is required for NLRP3 inflammasome activation in APCs...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28536970/mesoporous-silica-nanoparticle-coated-microneedle-arrays-for-intradermal-antigen-delivery
#15
Jing Tu, Guangsheng Du, M Reza Nejadnik, Juha Mönkäre, Koen van der Maaden, Paul H H Bomans, Nico A J M Sommerdijk, Bram Slütter, Wim Jiskoot, Joke A Bouwstra, Alexander Kros
PURPOSE: To develop a new intradermal antigen delivery system by coating microneedle arrays with lipid bilayer-coated, antigen-loaded mesoporous silica nanoparticles (LB-MSN-OVA). METHODS: Synthesis of MSNs with 10-nm pores was performed and the nanoparticles were loaded with the model antigen ovalbumin (OVA), and coated with a lipid bilayer (LB-MSN-OVA). The uptake of LB-MSN-OVA by bone marrow-derived dendritic cells (BDMCs) was studied by flow cytometry. The designed LB-MSN-OVA were coated onto pH-sensitive pyridine-modified microneedle arrays and the delivery of LB-MSN-OVA into ex vivo human skin was studied...
May 23, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28536468/il-27r-signaling-controls-myeloid-cells-accumulation-and-antigen-presentation-in-atherosclerosis
#16
Iuliia O Peshkova, Aliia R Fatkhullina, Zbigniew Mikulski, Klaus Ley, Ekaterina K Koltsova
Myeloid cells, key players in atherosclerosis, take up and present antigens, leading to systemic and local T cell activation. The recruitment and activation of immune cells to the aorta in atherosclerosis is regulated by adhesion molecules, chemokines and cytokines. IL-27R is an immunoregulatory signaling nod in autoimmune and infectious pathologies. IL-27R was shown to suppress T cells activation in atherosclerosis, however it's possible role in myeloid cell accumulation and activation is not understood. Here we demonstrate that Apoe (-/-) Il27ra (-/-) mice fed with "Western Diet" for 7 or 18 weeks developed significantly more atherosclerosis compared to Apoe (-/-) Il27ra (+/-) controls...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28535664/characterization-of-alphax-i-domain-binding-to-receptors-for-advanced-glycation-end-products-rage
#17
Dolgorsuren Buyannemekh, Sang-Uk Nham
The b2 integrins are cell surface transmembrane proteins regulating leukocyte functions, such as adhesion and migration. Two members of b2 integrin, aMb2 and aXb2, share the leukocyte distribution profile and integrin aXb2 is involved in antigen presentation in dendritic cells and transendothelial migration of monocytes and macrophages to atherosclerotic lesions. Receptor for advanced glycation end products (RAGE), a member of cell adhesion molecules, plays an important role in chronic inflammation and atherosclerosis...
May 24, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28534224/characterization-of-mhc-class-i-in-a-long-distance-migratory-wader-the-icelandic-black-tailed-godwit
#18
Sara Pardal, Anna Drews, José A Alves, Jaime A Ramos, Helena Westerdahl
The major histocompatibility complex (MHC) encodes proteins that are central for antigen presentation and pathogen elimination. MHC class I (MHC-I) genes have attracted a great deal of interest among researchers in ecology and evolution and have been partly characterized in a wide range of bird species. So far, the main focus has been on species within the bird orders Galliformes and Passeriformes, while Charadriiformes remain vastly underrepresented with only two species studied to date. These two Charadriiformes species exhibit striking differences in MHC-I characteristics and MHC-I diversity...
May 23, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28533776/reactivity-to-novel-autoantigens-in-patients-with-coexisting-central-nervous-system-demyelinating-disease-and-autoimmune-thyroid-disease
#19
Judith M Greer, Simon Broadley, Michael P Pender
Several lines of evidence suggest a definite and unique link between CNS demyelinating diseases and autoimmune thyroid disease (AITD). The aim of the current study was to systematically compare the clinical and laboratory features of patients with coexistent AITD and CNS demyelinating disease with those of patients with just CNS demyelinating disease. Forty-four patients with coexisting CNS demyelinating disease and AITD were identified and their clinical and radiological features were recorded. Blood and DNA were collected and tested for HLA type and for the response of T cells and antibodies to a variety of antigens...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28533311/converting-lymphoma-cells-into-potent-antigen-presenting-cells-for-interferon-induced-tumor-regression
#20
Jing Liao, Yan Luan, Zhenhua Ren, Xiaojuan Liu, Diyuan Xue, Hairong Xu, Zhichen Sun, Kaiting Yang, Hua Peng, Yang-Xin Fu
Anti-hCD20 is a therapeutic monoclonal antibody (mAb) that is clinically used to treat B-cell lymphoma. Some lymphomas are resistant to anti-hCD20; others relapse after treatment with anti-hCD20. Using a syngeneic immunocompetent mouse model, we observed that targeting lymphoma with interferon-alpha (IFNalpha) abolished resistance of B-cell lymphoma to anti-CD20 while limiting interferon (IFN)-associated systemic toxicity in the host. Control of tumors by a fusion of anti-CD20 and IFNalpha (anti-CD20-IFNalpha) depended on existing tumor-infiltrating CD8(+) T cells...
May 22, 2017: Cancer Immunology Research
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