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https://www.readbyqxmd.com/read/29045416/neonatal-immune-response-to-rhinovirus-a16-has-diminished-dendritic-cell-function-and-increased-b-cell-activation
#1
Amanda Barlow-Anacker, Yury Bochkov, James Gern, Christine M Seroogy
BACKGROUND: Rhinovirus infections during infancy account for the majority of respiratory illness health care utilization and are an associated risk factor for subsequent development of allergic asthma. Neonatal type I interferon production is diminished compared to adults after stimulation with TLR agonists. However, broad profiling of immune cell responses to infectious rhinovirus has not been undertaken and we hypothesized that additional immune differences can be identified in neonates...
2017: PloS One
https://www.readbyqxmd.com/read/29042497/a-single-dual-function-enzyme-controls-the-production-of-inflammatory-nod-agonist-peptidoglycan-fragments-by-neisseria-gonorrhoeae
#2
Jonathan D Lenz, Kathleen T Hackett, Joseph P Dillard
Neisseria gonorrhoeae gonococcus (GC) is a Gram-negative betaproteobacterium and causative agent of the sexually transmitted infection gonorrhea. During growth, GC releases lipooligosaccharide (LOS) and peptidoglycan (PG) fragments, which contribute significantly to the inflammatory damage observed during human infection. In ascending infection of human Fallopian tubes, inflammation leads to increased risk of ectopic pregnancy, pelvic inflammatory disease, and sterility. Of the PG fragments released by GC, most are disaccharide peptide monomers, and of those, 80% have tripeptide stems despite the observation that tetrapeptide stems make up 80% of the assembled cell wall...
October 17, 2017: MBio
https://www.readbyqxmd.com/read/29039348/the-impact-of-agonists-and-antagonists-of-tlr3-and-tlr9-on-concentrations-of-il-6-il10-and-sil-2r-in-culture-supernatants-of-peripheral-blood-mononuclear-cells-derived-from-patients-with-systemic-lupus-erythematosus
#3
Agnieszka Klonowska-Szymczyk, Liliana Kulczycka-Siennicka, Tadeusz Robak, Piotr Smolewski, Barbara Cebula-Obrzut, Ewa Robak
Toll-like receptors (TLR), especially TLR3, 7 and 9, play an important role in the pathogenesis of systemic lupus erythematosus (SLE). In our study blood was collected from 16 patients with SLE and from 8 healthy volunteers. Concentrations of IL-6, IL-10 and sIL-2R were measured by ELISA in mononuclear cell culture supernatant after 24 hours of stimulation by agonists and antagonists of TLR3 and 9 (for TLR3-poli I/C, resveratrol and for TLR9-ODN2006, IRS 945). Stimulation of TLR9 by ODN2006 led to an increase of IL-6 concentration in cell culture supernatants from the cells of healthy volunteers compared with unstimulated cells from controls...
October 13, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/29031697/ubiquitin-modifying-enzymes-and-regulation-of-the-inflammasome
#4
REVIEW
Michael G Kattah, Barbara A Malynn, Averil Ma
Ubiquitin and ubiquitin-modifying enzymes play critical roles in a wide variety of intracellular signaling pathways. Inflammatory signaling cascades downstream of TNF, TLR agonists, antigen receptor cross-linking, and cytokine receptors, all rely on ubiquitination events to direct subsequent immune responses. In the past several years, inflammasome activation and subsequent signal transduction have emerged as an excellent example of how ubiquitin signals control inflammatory responses. Inflammasomes are multiprotein signaling complexes that ultimately lead to caspase activation and release of the interleukin-1 (IL-1) family members, IL-1β and IL-18...
October 12, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28993635/response-of-human-periodontal-ligament-stem-cells-to-ifn-%C3%AE-and-tlr-agonists
#5
Oleh Andrukhov, Johanna Sang-A Hong, Olena Andrukhova, Alice Blufstein, Andreas Moritz, Xiaohui Rausch-Fan
Periodontal ligament stem cells similarly to the mesenchymal stem cells of other tissues possess immunomodulatory properties, which are regulated by different cytokines, particularly by interferon-γ (IFN-γ). In contrast, less information is provided about the effect of toll-like receptors ligand on immunomodulatory properties of these cells. In the present study we investigated the response of human periodontal ligament stem cells (hPDLSCs) in response to simultaneous stimulation with IFN-γ and toll-like receptor (TLR) agonists...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28987878/co-delivery-of-nucleoside-modified-mrna-and-tlr-agonists-for-cancer-immunotherapy-restoring-the-immunogenicity-of-immunosilent-mrna
#6
Rein Verbeke, Ine Lentacker, Laura Wayteck, Karine Breckpot, Mieke Van Bockstal, Benedicte Descamps, Christian Vanhove, Stefaan C De Smedt, Heleen Dewitte
This study reports on the design of mRNA and adjuvant-loaded lipid nanoparticles for therapeutic cancer vaccination. The use of nucleoside-modified mRNA has previously been shown to improve the translational capacity and safety of mRNA-therapeutics, as it prevents the induction of type I interferons (IFNs). However, type I IFNs were identified as the key molecules that trigger the activation of antigen presenting cells, and as such drive T cell immunity. We demonstrate that nucleoside-modified mRNA can be co-delivered with the clinically approved TLR agonist monophosphoryl lipid A (MPLA)...
October 5, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28987803/long-acting-%C3%AE-2-adrenoreceptor-agonists-suppress-type-1-interferon-expression-in-human-plasmacytoid-dendritic-cells-via-epigenetic-regulation
#7
Chang-Hung Kuo, San-Nan Yang, Yi-Giien Tsai, Chong-Chao Hsieh, Wei-Ting Liao, Li-Chen Chen, Min-Sheng Lee, Hsuan-Fu Kuo, Ching-Hsiung Lin, Chih-Hsing Hung
The combination of inhaled long-acting β2-adrenoreceptor (LABA) and inhaled glucocorticoid (ICS) is a major therapy for asthma. However, the increased risk of infection is still a concern. Plasmacytoid dendritic cells (pDCs) are the predominant cells producing type 1 interferon (IFN) against infection. The effect of LABA/ICS on type 1 IFN expression in human pDCs is unknown. Circulating pDCs were isolated from healthy human subjects and were pretreated with glucocorticoid (GCS), LABA or a cAMP analog, and were stimulated with Toll-like receptor (TLR) agonist CpG (TLR9) or imiquimod (TLR7) in the presence of IL-3...
October 4, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28970832/use-of-toll-like-receptor-agonists-to-induce-ectopic-lymphoid-structures-in-myasthenia-gravis-mouse-models
#8
Marieke Robinet, Bérengère Villeret, Solène Maillard, Mélanie A Cron, Sonia Berrih-Aknin, Rozen Le Panse
Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction. MG symptoms are characterized by muscle weaknesses. The thymus of MG patients is very often abnormal and possesses all the characteristics of tertiary lymphoid organs such as neoangiogenesis processes, overexpression of inflammatory cytokines and chemokines, and infiltration of B lymphocytes leading to ectopic germinal center (GC) development. We previously demonstrated that injections of mice with polyinosinic-polycytidylic acid [Poly(I:C)], a synthetic double-stranded RNA mimicking viral infection, induce thymic changes and trigger MG symptoms...
2017: Frontiers in Immunology
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
#9
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...
September 27, 2017: Molecular Immunology
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
#10
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/28951731/minimal-sex-differential-modulation-of-reactivity-to-pathogens-and-toll-like-receptor-ligands-following-infant-bacillus-calmette-gu%C3%A3-rin-russia-vaccination
#11
Fatoumatta Darboe, Jane U Adetifa, John Reynolds, Safayet Hossin, Magdalena Plebanski, Mihai G Netea, Sarah L Rowland-Jones, Jayne S Sutherland, Katie L Flanagan
Bacillus Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis, has been shown to provide heterologous protection against unrelated pathogens and enhance antibody responses to several routine expanded program on immunization (EPI) vaccines. Understanding these heterologous effects is important for the development of optimal vaccination strategies. We set out to assess the effect of vaccination with BCG Russia of 6-week-old infants on in vitro reactivity to a panel of toll-like receptor (TLR) agonists (TLR2, 4, and 7/8) and heat-killed pathogens [Streptococcus pneumoniae, Candida albicans (CA), and Escherichia coli], and antibody responses to other EPI vaccines compared to BCG naïve infants...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28951424/myd88-is-required-for-disease-development-in-a-primary-sj%C3%A3-gren-s-syndrome-mouse-model
#12
Jeremy Kiripolsky, Liam G McCabe, Daniel P Gaile, Jill M Kramer
Sjögren's syndrome (SS) is an autoimmune disease that often results in diminished exocrine gland function. SS patients also experience systemic disease manifestations, including hypergammaglobulinemia and pulmonary and renal pathoses. MyD88 is a ubiquitously expressed adaptor molecule used by all immune cells that is required for IL-1 receptor (IL-1R), IL-18R, and most TLR signaling. The precise role of MyD88 in SS has not been evaluated, although this adaptor is critical for development of lupus, a related autoimmune disease...
September 26, 2017: Journal of Leukocyte Biology
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
#13
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/28931759/combination-immunotherapy-with-tlr-agonists-and-checkpoint-inhibitors-suppresses-head-and-neck-cancer
#14
Fumi Sato-Kaneko, Shiyin Yao, Alast Ahmadi, Shannon S Zhang, Tadashi Hosoya, Megan M Kaneda, Judith A Varner, Minya Pu, Karen S Messer, Cristiana Guiducci, Robert L Coffman, Kazutaka Kitaura, Takaji Matsutani, Ryuji Suzuki, Dennis A Carson, Tomoko Hayashi, Ezra Ew Cohen
Checkpoint inhibitors have demonstrated efficacy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). However, the majority of patients do not benefit from these agents. To improve the efficacy of checkpoint inhibitors, intratumoral (i.t.) injection with innate immune activators, TLR7 and TLR9 agonists, were tested along with programmed death-1 receptor (PD-1) blockade. The combination therapy suppressed tumor growth at the primary injected and distant sites in human papillomavirus-negative (HPV-negative) SCC7 and MOC1, and HPV-positive MEER syngeneic mouse models...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28924041/irak4-kinase-activity-controls-toll-like-receptor-induced-inflammation-through-the-transcription-factor-irf5-in-primary-human-monocytes
#15
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 the transcription factor IRF5, a transcription factor implicated in the pathogenesis of multiple autoimmune diseases...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28921471/tlr-agonists-as-adjuvants-for-cancer-vaccines
#16
Ji-Kun Li, Jesse J Balic, Liang Yu, Brendan Jenkins
Toll-like receptors (TLRs) are one of the best characterised families of pattern recognition receptors (PRRs) and play a critical role in the host defence to infection. Accumulating evidence indicates that TLRs also participate in maintaining tissue homeostasis by controlling inflammation and tissue repair, as well as promoting antitumour effects via activation and modulation of adaptive immune responses. TLR agonists have successfully been exploited to ameliorate the efficacy of various cancer therapies. In this chapter, we will discuss the rationales of using TLR agonists as adjuvants to cancer treatments and summarise the recent findings of preclinical and clinical studies of TLR agonist-based cancer therapies...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28901470/tlr5-7-mediated-pi3k-activation-triggers-epithelial-mesenchymal-transition-of-ovarian-cancer-cells-through-wave3-dependent-mesothelin-or-oct4-sox2-expression
#17
Ga Bin Park, Daejin Kim
Toll-like receptor (TLR)-mediated signaling induces cell migration or invasion in several tumors and various stages of cancer. Interactions of mesothelin, a 40-kDa cell surface glycoprotein, with cancer antigen 125 (CA125) is associated with drug resistance, metastasis, and poor clinical outcome of ovarian cancer patients. In this study, we examined the role of TLR5 and TLR7 in the metastasis of ovarian cancer through the induction of mesothelin/CA125 expression and investigated its underlying mechanism. TLR5 agonist (flagellin) and TLR7 agonist (imiquimod) upregulated mesenchymal phenotypes and produced epithelial-mesenchymal transition (EMT)-related cytokines in the SKOV3 cells; however, TLR7 expressing CaOV3 cells had no response to the specific ligand, imiquimod, for enhancing its EMT processes...
November 2017: Oncology Reports
https://www.readbyqxmd.com/read/28894754/natural-modulators-of-endosomal-toll-like-receptor-mediated-psoriatic-skin-inflammation
#18
REVIEW
Chao-Yang Lai, Yu-Wen Su, Kuo-I Lin, Li-Chung Hsu, Tsung-Hsien Chuang
Psoriasis is a chronic inflammatory autoimmune disease that can be initiated by excessive activation of endosomal toll-like receptors (TLRs), particularly TLR7, TLR8, and TLR9. Therefore, inhibitors of endosomal TLR activation are being investigated for their ability to treat this disease. The currently approved biological drugs adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, and secukizumab are antibodies against effector cytokines that participate in the initiation and development of psoriasis...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28894350/short-term-regulation-of-fc%C3%AE-r-mediated-phagocytosis-by-tlrs-in-macrophages-participation-of-5-lipoxygenase-products
#19
Carla da S Pinheiro, Ana Paula T Monteiro, Fabiano F Dutra, Marcelo T Bozza, Marc Peters-Golden, Claudia F Benjamim, Claudio Canetti
TLRs recognize a broad spectrum of microorganism molecules, triggering a variety of cellular responses. Among them, phagocytosis is a critical process for host defense. Leukotrienes (LTs), lipid mediators produced from 5-lipoxygenase (5-LO) enzyme, increase FcγR-mediated phagocytosis. Here, we evaluated the participation of TLR2, TLR3, TLR4, and TLR9 in FcγR-mediated phagocytosis and whether this process is modulated by LTs. Rat alveolar macrophages (AMs), murine bone marrow-derived macrophages (BMDMs), and peritoneal macrophages (PMs) treated with TLR2, TLR3, and TLR4 agonists, but not TLR9, enhanced IgG-opsonized sheep red blood cell (IgG-sRBC) phagocytosis...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28891637/bioconjugation-approaches-to-producing-subunit-vaccines-composed-of-protein-or-peptide-antigens-and-covalently-attached-toll-like-receptor-ligands
#20
Zhenghui Xu, Peter Michael Moyle
Traditional vaccines derived from attenuated or inactivated pathogens are effective at inducing antibody-based protective immune responses but tend to be highly reactogenic, causing notable adverse effects. Vaccines with superior safety profiles can be produced by subunit approaches, utilizing molecularly defined antigens (e.g., proteins and polysaccharides). These antigens, however, often elicit poor immunological responses, necessitating the use of adjuvants. Immunostimulatory adjuvants have the capacity to activate antigen presenting cells directly through specific receptors (e...
September 22, 2017: Bioconjugate Chemistry
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