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https://www.readbyqxmd.com/read/29344995/activation-of-human-cd141-and-cd1c-dendritic-cells-in-vivo-with-combined-tlr-3-and-tlr-7-8-ligation
#1
Frances E Pearson, Karshing Chang, Yoshihito Minoda, Ingrid M Leal Rojas, Oscar L Haigh, Ghazal Daraj, Kirsteen M Tullett, Kristen J Radford
Mice reconstituted with human hematopoietic stem cells are valuable models to study aspects of the human immune system in vivo. We describe a humanized mouse model (hu mice) in which fully functional human CD141+ and CD1c+ myeloid and CD123+ plasmacytoid dendritic cells (DC) develop from human cord blood CD34+ cells in immunodeficient mice. CD141+ DC are the human equivalents of murine CD8+ /CD103+ DC which are essential for the induction of tumor-inhibitory cytotoxic T lymphocyte (CTL) responses, making them attractive targets to exploit for the development of new cancer immunotherapies...
January 18, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29313026/transcutaneous-pollinosis-immunotherapy-using-a-solid-in-oil-nanodispersion-system-carrying-t-cell-epitope-peptide-and-r848
#2
Momoko Kitaoka, Ayaka Naritomi, Yoshinori Kawabe, Masamichi Kamihira, Noriho Kamiya, Masahiro Goto
Antigen-specific immunotherapy is the only curative approach for the treatment of allergic diseases such as Japanese cedar pollinosis. Immunotherapy using a T cell epitope vaccine in combination with the adjuvant R848 is of particular interest as a safe and effective approach to treat allergic diseases. Herein, we propose a simple and easy to handle vaccine administration method using the original solid-in-oil (S/O) nanodispersion system that permeates through the skin. The S/O nanodispersion system is composed of nanoparticles of hydrophilic molecules surrounded with hydrophobic surfactants that are dispersed in an oil vehicle...
March 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/29261777/self-extracellular-rna-acts-in-synergy-with-exogenous-danger-signals-to-promote-inflammation
#3
Frederik Noll, Jonas Behnke, Silke Leiting, Kerstin Troidl, Gustavo Teixeira Alves, Holger Müller-Redetzky, Klaus T Preissner, Silvia Fischer
Self-extracellular RNA (eRNA), released from stressed or injured cells upon various pathological situations such as ischemia-reperfusion-injury, has been shown to act as an alarmin by inducing procoagulatory and proinflammatory responses. In particular, M1-polarization of macrophages by eRNA resulted in the expression and release of a variety of cytokines, including tumor necrosis factor (TNF)-α or interleukin-6 (IL-6). The present study now investigates in which way self-eRNA may influence the response of macrophages towards various Toll-like receptor (TLR)-agonists...
2017: PloS One
https://www.readbyqxmd.com/read/29181691/irreversible-phenotypic-perturbation-and-functional-impairment-of-b-cells-during-hiv-1-infection
#4
Jingjing Yan, Shuye Zhang, Jun Sun, Jianqing Xu, Xiaoyang Zhang
Human immunodeficiency virus type 1 (HIV-1) infection can damage humoral immunity. The knowledge of B cell perturbations during chronic HIV-1 infection and their recovery after combined antiretroviral therapy (cART) is not complete yet, and thus attempts to further improve humoral immunity are impeded. In this study, an HIV-1 chronically infected cohort with similar demographics, infection history, genetic background, and HIV-1 genotype was established to probe B cell perturbations. Results showed that the B cells from this cohort were highly activated and prone to cell death, and B cell compartments were altered significantly...
November 27, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/29181417/toll-like-receptor-ligand-induced-liver-injury-in-d-galactosamine-sensitized-mice-differences-between-tlr7-8-and-tlr9-ligands-cytokine-patterns-and-cross-tolerance-induction-by-tlr2-ligand-pretreatment
#5
Reiko Seki
Administration of Toll-like receptor ligands (TLRLs) is known to cause liver injury in D-galN-sensitized mice. In the present study, we aimed to complement preceding reports on the TLRL/D-galN system by analyzing comparisons among TLRLs, mouse strain dependence, effects on serum levels of cytokines, and effects of sequential administrations of different TLRLs. In a preliminary set of analyses, we first confirmed that liver failure can be induced by diverse TLRLs, including LTA and R848 in combination with D-galN...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29179132/rational-incorporation-of-molecular-adjuvants-into-a-hybrid-nanoparticle-based-nicotine-vaccine-for-immunotherapy-against-nicotine-addiction
#6
Zongmin Zhao, Brian Harris, Yun Hu, Theresa Harmon, Paul R Pentel, Marion Ehrich, Chenming Zhang
Current clinically-tested nicotine vaccines have yet shown enhanced smoking cessation efficacy due to their low immunogenicity. Achieving a sufficiently high immunogenicity is a necessity for establishing a clinically-viable nicotine vaccine. This study aims to facilitate the immunogenicity of a hybrid nanoparticle-based nicotine vaccine by rationally incorporating toll-like receptor (TLR)-based adjuvants, including monophosphoryl lipid A (MPLA), Resiquimod (R848), CpG oligodeoxynucleotide 1826 (CpG ODN 1826), and their combinations...
November 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/29163495/human-cd141-dendritic-cell-and-cd1c-dendritic-cell-undergo-concordant-early-genetic-programming-after-activation-in-humanized-mice-in-vivo
#7
Yoshihito Minoda, Isaac Virshup, Ingrid Leal Rojas, Oscar Haigh, Yide Wong, John J Miles, Christine A Wells, Kristen J Radford
Human immune cell subsets develop in immunodeficient mice following reconstitution with human CD34(+) hematopoietic stem cells. These "humanized" mice are useful models to study human immunology and human-tropic infections, autoimmunity, and cancer. However, some human immune cell subsets are unable to fully develop or acquire full functional capacity due to a lack of cross-reactivity of many growth factors and cytokines between species. Conventional dendritic cells (cDCs) in mice are categorized into cDC1, which mediate T helper (Th)1 and CD8(+) T cell responses, and cDC2, which mediate Th2 and Th17 responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29150086/the-ex-vivo-toll-like-receptor-7-tolerance-induction-in-donor-lymphocytes-prevents-murine-acute-graft-versus-host-disease
#8
Nikolaos Zogas, Garyfalia Karponi, Fotios Iordanidis, Stylianos Malasidis, Vasilios Paraskevas, Anastasia Papadopoulou, Zaharias George Scouras, Achilles Anagnostopoulos, Evangelia Yannaki
BACKGROUND AIMS: Acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation, mediated by alloreactive donor T cells. Toll-like receptors (TLRs), a family of conserved pattern-recognition receptors (PRRs), represent key players in donors' T-cell activation during aGVHD; however, a regulatory, tolerogenic role for certain TLRs has been recognized in a different context. We investigated whether the ex vivo-induced TLR-2,-4,-7 tolerance in donor cells could prevent alloreactivity in a mismatched transplantation model...
November 14, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29138398/characterization-of-macrophages-from-schizophrenia-patients
#9
Paul R Ormel, Hans C van Mierlo, Manja Litjens, Miriam E van Strien, Elly M Hol, René S Kahn, Lot D de Witte
Genetic, epidemiological and post mortem studies have described an association between schizophrenia (SCZ) and the immune system. Microglia, the tissue-resident macrophages of the brain, not only play an essential role in inflammatory processes, but also in neurodevelopment and synapse refinement. It has therefore been hypothesized that aberrant functioning of these myeloid immune cells is involved in SCZ pathogenesis. Until now cellular research into the role of myeloid cells in SCZ has been limited to monocytes and functional assays are lacking...
November 14, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/29129789/dual-ph-responsive-multifunctional-nanoparticles-for-targeted-treatment-of-breast-cancer-by-combining-immunotherapy-and-chemotherapy
#10
Yuanyuan Liu, Linan Qiao, Sipei Zhang, Guoyun Wan, Bowei Chen, Ping Zhou, Ning Zhang, Yinsong Wang
In the present study, a dual pH-responsive multifunctional nanoparticle system was designed for combining immunotherapy and chemotherapy to treat breast cancer through targeting immune cells and cancer cells. A proven anti-tumor immune regulator, R848, was encapsulated with poly(L-histidine) (PHIS) to form PHIS/R848 nanocores. Doxorubicin (DOX) was conjugated to hyaluronic acid (HA) through an acid-cleavable hydrazone bond linkage to synthesize polymeric prodrug HA-DOX, which was subsequently coated outside PHIS/R848 nanocores to form HA-DOX/PHIS/R848 nanoparticles...
November 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29097235/unc93b1-is-essential-for-cytokine-activation-of-five-pamps-in-the-orange-spotted-grouper-epinephelus-coioides
#11
Yaosi Liang, Yu Wang, Liangge He, Jianan He, Wan Peng, Libin Zhou, Yong Zhang, Haifa Zhang, Herong Shi, Haoran Lin, Danqi Lu
Toll-like receptors (TLRs) are important innate immune receptors that recognize multiple pathogen-associated molecular patterns (PAMPs) and activate the immune responses to resist the invasion of pathogens. Many TLRs need assistance from trafficking chaperones to transport to the specific cell compartments and then are processed before they are activated. In this study, we identified an important trafficking chaperone, Unc-93 homolog B1 (unc93b1), from the Epinephelus coioides (orange-spotted grouper). The deduced protein sequence of Eco...
October 31, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29079801/development-of-a-curative-therapeutic-vaccine-theravac-for-the-treatment-of-large-established-tumors
#12
Yingjie Nie, De Yang, Anna Trivett, Zhen Han, Haiyun Xin, Xin Chen, Joost J Oppenheim
Harnessing immune system to treat cancer requires simultaneous generation of tumor-specific CTLs and curtailment of tumor immunosuppressive environment. Here, we developed an immunotherapeutic regimen capable of eliminating large established mouse tumors using HMGN1, a DC-activating TLR4 agonist capable of inducing anti-tumor immunity. Intratumoral delivery of HMGN1 with low dose of Cytoxan cured mice bearing small (∅ ≈ 0.5 cm), but not large (∅ ≈ 1.0 cm) CT26 tumors. Screening for activators capable of synergizing with HMGN1 in activating DC identified R848...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29053867/molecular-cloning-and-functional-analysis-of-peafowl-pavo-cristatus-toll-like-receptor-7
#13
H Song, M Zhang, W Gao, L Wu, G Li
In order to clone the peafowl (Pavo cristatus) Toll-like receptor 7 (TLR7) gene and study its biological function, the peafowl TLR7 coding sequences (CDS) were amplified by PCR of cDNA from the whole spleen of peafowl. The full-length sequence of the peafowl TLR7 gene CDS is 3,141 bp and encodes a 1,046-amino acid protein with a classic TLR composition of 16 leucine-rich repeats (LRR). Insertions of amino acids were found at position 15 of LRR2, LRR5, LRR7, LRR9, LRR11, LRR12, LRR14, and LRR15; and position 10 of LRR11...
October 5, 2017: Poultry Science
https://www.readbyqxmd.com/read/28967521/adjuvanting-an-inactivated-influenza-vaccine-with-conjugated-r848-improves-the-level-of-antibody-present-at-6months-in-a-nonhuman-primate-neonate-model
#14
Beth C Holbrook, Ralph B D'Agostino, S Tyler Aycock, Matthew J Jorgensen, Mallinath B Hadimani, S Bruce King, Martha A Alexander-Miller
Generation of a potent antibody response that can be sustained over time is highly challenging in young infants. Our previous studies using a nursery-reared nonhuman primate model identified R848 conjugated to inactivated influenza virus as a highly immunogenic vaccine for neonates. Here we determined the effectiveness of this vaccine in mother-reared infants as well as its ability to promote improved responses at 6months compared to vaccination in the absence of R848. In agreement with our nursery study, R848 conjugated to influenza virus induced a higher antibody response in neonates compared to the non-adjuvanted vaccine...
October 27, 2017: Vaccine
https://www.readbyqxmd.com/read/28963929/evaluation-of-the-adjuvant-effect-of-agonists-of-toll-like-receptor-4-and-7-8-in-a-vaccine-against-leishmaniasis-in-balb-c-mice
#15
Mosayeb Rostamian, Hamid M Niknam
There is no effective vaccine against human leishmaniasis. Achieving successful vaccines seems to need powerful adjuvants. Separate or combined use of toll like receptor (TLR) agonists as adjuvant is a promising approach in Leishmania vaccine research. In present study, we evaluated adjuvant effect of separate or combined use of a TLR7/8 agonist, R848 and a TLR4 agonist, monophosphoryl lipid A (MPL) beside soluble Leishmania antigen (SLA) in BALB/c mice. Mice were vaccinated three times by SLA with separate or combined TLR7/8 and TLR4 agonists and were then challenged by Leishmania major...
November 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28958808/human-innate-responses-and-adjuvant-activity-of-tlr-ligands-in-vivo-in-mice-reconstituted-with-a-human-immune-system
#16
Liang Cheng, Zheng Zhang, Guangming Li, Feng Li, Li Wang, Liguo Zhang, Sandra M Zurawski, Gerard Zurawski, Yves Levy, Lishan Su
TLR ligands (TLR-Ls) represent a class of novel vaccine adjuvants. However, their immunologic effects in humans remain poorly defined in vivo. Using a humanized mouse model with a functional human immune system, we investigated how different TLR-Ls stimulated human innate immune response in vivo and their applications as vaccine adjuvants for enhancing human cellular immune response. We found that splenocytes from humanized mice showed identical responses to various TLR-Ls as human PBMCs in vitro. To our surprise, various TLR-Ls stimulated human cytokines and chemokines differently in vivo compared to that in vitro...
October 27, 2017: Vaccine
https://www.readbyqxmd.com/read/28955328/co-delivery-of-dual-toll-like-receptor-agonists-and-antigen-in-poly-lactic-co-glycolic-acid-polyethylenimine-cationic-hybrid-nanoparticles-promote-efficient-in-vivo-immune-responses
#17
Mahboubeh Ebrahimian, Maryam Hashemi, Mohsen Maleki, Gholamreza Hashemitabar, Khalil Abnous, Mohammad Ramezani, Alireza Haghparast
Strategies to design delivery vehicles are critical in modern vaccine-adjuvant development. Nanoparticles (NPs) encapsulating antigen(s) and adjuvant(s) are promising vehicles to deliver antigen(s) and adjuvant(s) to antigen-presenting cells (APCs), allowing optimal immune responses against a specific pathogen. In this study, we developed a novel adjuvant delivery approach for induction of efficient in vivo immune responses. Polyethylenimine (PEI) was physically conjugated to poly(lactic-co-glycolic) acid (PLGA) to form PLGA/PEI NPs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28940186/an-r848-adjuvanted-influenza-vaccine-promotes-early-activation-of-b-cells-in-the-draining-lymph-node-of-nonhuman-primate-neonates
#18
Beth C Holbrook, S Tyler Aycock, Emily Machiele, Elene Clemens, Danielle Gries, Matthew J Jorgensen, Mallinath B Hadimani, S Bruce King, Martha A Alexander-Miller
Impaired immune responsiveness is a significant barrier to vaccination of neonates. By way of example, the low seroconversion observed following influenza vaccination has led to restriction of its use to infants over 6 months of age, leaving younger infants vulnerable to infection. Our previous studies using a nonhuman primate neonate model demonstrated that the immune response elicited following vaccination with inactivated influenza virus could be robustly increased by inclusion of the TLR agonist flagellin or R848, either delivered individually or in combination...
September 22, 2017: Immunology
https://www.readbyqxmd.com/read/28924041/irak4-kinase-activity-controls-toll-like-receptor-induced-inflammation-through-the-transcription-factor-irf5-in-primary-human-monocytes
#19
Leah Cushing, Aaron Winkler, Scott A Jelinsky, Katherine Lee, Wouter Korver, Rachael Hawtin, Vikram R Rao, Margaret Fleming, Lih-Ling Lin
Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a critical role in innate immune signaling by Toll-like receptors (TLRs), and loss of IRAK4 activity in mice and humans increases susceptibility to bacterial infections and causes defects in TLR and IL1 ligand sensing. However, the mechanism by which IRAK4 activity regulates the production of downstream inflammatory cytokines is unclear. Using transcriptomic and biochemical analyses of human monocytes treated with a highly potent and selective inhibitor of IRAK4, we show that IRAK4 kinase activity controls the activation of interferon regulatory factor 5 (IRF5), a transcription factor implicated in the pathogenesis of multiple autoimmune diseases...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28921509/baff-augments-iga2-and-il-10-production-by-tlr7-8-stimulated-total-peripheral-blood-b%C3%A2-cells
#20
Gerco den Hartog, Thijs L J van Osch, Martijn Vos, Ben Meijer, Huub F J Savelkoul, R J Joost van Neerven, Sylvia Brugman
Class-switching of B cells to IgA can be induced via both T-cell-dependent and T-cell-independent mechanisms. IgA is most predominantly produced mucosally and is important for combating infections and allergies. In contrast to mice, humans have two forms of IgA; IgA1 and IgA2 with diverse tissue distribution. In early life, IgA levels might be sub-optimal especially during the fall season when bacterial and viral infections are more common. Therefore, we investigated using human B cells whether T-cell-independent factors -promoting cell survival, class switching and immunoglobulin secretion- BAFF, APRIL, IL-10 and retinoic acid can boost IgA production in the context of viral or bacterial infection...
September 17, 2017: European Journal of Immunology
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