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https://www.readbyqxmd.com/read/28724768/synthetic-tlr4-and-tlr7-ligands-work-additively-via-myd88-to-induce-protective-antiviral-immunity-in-mice
#1
Peter H Goff, Tomoko Hayashi, Wenqian He, Shiyin Yao, Howard B Cottam, Gene S Tan, Brian Crain, Florian Krammer, Karen Messer, Minya Pu, Dennis A Carson, Peter Palese, Maripat Corr
We have previously demonstrated that the combination of synthetic small molecule Toll-like receptor 4 (TLR4) and TLR7 ligands is a potent adjuvant for recombinant influenza virus hemagglutinin, inducing rapid and sustained immunity protective against influenza viruses in homologous, heterologous and heterosubtypic murine challenge models. Combining TLR4 and TLR7 ligands balances Th1/Th2-type immune responses for long-lived cellular and neutralizing humoral immunity against the viral hemagglutinin. Here, we demonstrate that the protective response induced in mice by this combined adjuvant is dependent upon TLR4 and TLR7 signaling via myeloid differentiation primary response gene 88 (MyD88), indicating that the adjuvants function in vivo via their known receptors with negligible off-target effects to induce protective immunity...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28720097/a-versatile-papaya-mosaic-virus-papmv-vaccine-platform-based-on-sortase-mediated-antigen-coupling
#2
Ariane Thérien, Mikaël Bédard, Damien Carignan, Gervais Rioux, Louis Gauthier-Landry, Marie-Ève Laliberté-Gagné, Marilène Bolduc, Pierre Savard, Denis Leclerc
BACKGROUND: Flexuous rod-shaped nanoparticles made of the coat protein (CP) of papaya mosaic virus (PapMV) have been shown to trigger innate immunity through engagement of toll-like receptor 7 (TLR7). PapMV nanoparticles can also serve as a vaccine platform as they can increase the immune response to fused peptide antigens. Although this approach shows great potential, fusion of antigens directly to the CP open reading frame (ORF) is challenging because the fused peptides can alter the structure of the CP and its capacity to self assemble into nanoparticles-a property essential for triggering an efficient immune response to the peptide...
July 18, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28715461/tlr1-10-nf-%C3%AE%C2%BAb-and-p53-expression-is-increased-in-oral-lichenoid-disease
#3
Peter Rusanen, Emilia Marttila, Johanna Uittamo, Jaana Hagström, Tuula Salo, Riina Rautemaa-Richardson
Toll-like receptors (TLRs) and nuclear factor-κB (NF-κB) in keratinocytes play an important role in dermatological autoimmune diseases. Tumour suppressor protein p53 regulates TLR expression. The aim of this study was to compare the expression of TLR1-TLR10, p53 and NF-κB in patients with oral lichenoid disease (OLD) with healthy mucosa. Oral mucosal biopsies from 24 patients with OLD and 26 healthy controls (HC) were analysed for the expression of TLR1-TLR10, NF-κB and p53 by immunohistochemistry. The expression of all TLRs was increased in OLD epithelia compared to HC samples and the difference was significant in TLR1, TLR3, TLR4, TLR5, TLR6 and TLR7...
2017: PloS One
https://www.readbyqxmd.com/read/28712404/-polymorphisms-of-tlr7-rs3853839-and-rs179010-are-associated-with-susceptibility-to-and-severity-of-hand-foot-and-mouth-disease-caused-by-enterovirus-71-in-male-children
#4
Yaping Li, Song Zhai, Mei Li, Yuan Wang, Tong Lu, Huiling Deng, Xin Zhang, Shuangsuo Dang
Objective To investigate whether the polymorphisms of TLR7/MyD88 signaling pathway is associated with the susceptibility to and severity of hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) in children. Methods We collected 180 EV71 HFMD cases and 201 healthy controls from both the Second Affiliated Hospital of Xi'an Jiaotong University and Xi'an Children's Hospital. The genotypes including rs3853839, rs179010 of TLR7, and rs7744 of MyD88 were detected in the 381 samples by SNPscan kit. Results The susceptibility risk (OR=2...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28707750/arterial-immune-protein-expression-demonstrates-the-complexity-of-immune-responses-in-kawasaki-disease-arteritis
#5
Scott A Cameron, Steven M White, David Arrollo, Stanford T Shulman, Anne H Rowley
BACKGROUND: A more complete understanding of immune-mediated damage to the coronary arteries in children with Kawasaki disease (KD) is required for improvements in patient treatment and outcomes. We recently reported the transcriptional profile of KD coronary arteritis, and here sought to determine protein expression of transcriptionally upregulated immune genes in KD coronary arteries from the first two months after disease onset. METHODS: We examined the coronary arteries of 12 fatal KD cases and 13 childhood controls for expression of a set of proteins whose genes were highly upregulated in the KD coronary artery transcriptome: allograft inflammatory factor 1 (AIF1), interleukin 18 (IL-18), CD74, CD1c, CD20 (MS4A1), Toll-like receptor 7 (TLR7), and Z-DNA binding protein 1 (ZBP1)...
July 14, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28701733/endosomal-nox2-oxidase-exacerbates-virus-pathogenicity-and-is-a-target-for-antiviral-therapy
#6
Eunice E To, Ross Vlahos, Raymond Luong, Michelle L Halls, Patrick C Reading, Paul T King, Christopher Chan, Grant R Drummond, Christopher G Sobey, Brad R S Broughton, Malcolm R Starkey, Renee van der Sluis, Sharon R Lewin, Steven Bozinovski, Luke A J O'Neill, Tim Quach, Christopher J H Porter, Doug A Brooks, John J O'Leary, Stavros Selemidis
The imminent threat of viral epidemics and pandemics dictates a need for therapeutic approaches that target viral pathology irrespective of the infecting strain. Reactive oxygen species are ancient processes that protect plants, fungi and animals against invading pathogens including bacteria. However, in mammals reactive oxygen species production paradoxically promotes virus pathogenicity by mechanisms not yet defined. Here we identify that the primary enzymatic source of reactive oxygen species, NOX2 oxidase, is activated by single stranded RNA and DNA viruses in endocytic compartments resulting in endosomal hydrogen peroxide generation, which suppresses antiviral and humoral signaling networks via modification of a unique, highly conserved cysteine residue (Cys98) on Toll-like receptor-7...
July 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28696254/human-monocyte-subsets-are-transcriptionally-and-functionally-altered-in-aging-in-response-to-pattern-recognition-receptor-agonists
#7
Talibah U Metcalf, Peter A Wilkinson, Mark J Cameron, Khader Ghneim, Cindy Chiang, Anne M Wertheimer, John B Hiscott, Janko Nikolich-Zugich, Elias K Haddad
Age-related alterations in immunity have been linked to increased incidence of infections and decreased responses to vaccines in the aging population. Human peripheral blood monocytes are known to promote Ag presentation and antiviral activities; however, the impact of aging on monocyte functions remains an open question. We present an in-depth global analysis examining the impact of aging on classical (CD14(+)CD16(-)), intermediate (CD14(+)CD16(+)), and nonclassical (CD14(dim)CD16(+)) monocytes. Monocytes sorted from nonfrail healthy adults (21-40 y) and old (≥65 y) individuals were analyzed after stimulation with TLR4, TLR7/8, and retinoic acid-inducible gene I agonists...
July 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28690034/interplay-of-inflammatory-gene-expression-in-pericytes-following-japanese-encephalitis-virus-infection
#8
Cheng-Yi Chang, Jian-Ri Li, Yen-Chuan Ou, Shih-Yi Lin, Ya-Yu Wang, Wen-Ying Chen, Yu-Hui Hu, Ching-Yi Lai, Chen-Jung Chang, Chun-Jung Chen
Neuroinflammation is a pathological hallmark and has been implicated in the pathogenesis of Japanese encephalitis. Although brain pericytes show regulatory effects on neuroinflammation, their involvement in Japanese encephalitis-associated neuroinflammation is not understood. Here, we demonstrated that brain microvascular pericytes could be an alternative cellular source for the induction and/or amplification of neuroinflammation caused by Japanese encephalitis virus (JEV) infection. Infection of cultured pericytes with JEV caused profound production of IL-6, RANTES, and prostaglandin E2 (PGE2)...
July 6, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28689773/the-toll-like-receptor-ligands-hiltonol-%C3%A2-polyiclc-and-imiquimod-effectively-activate-antigen-specific-immune-responses-in-tasmanian-devils-sarcophilus-harrisii
#9
Amanda L Patchett, Cesar Tovar, Lynn M Corcoran, A Bruce Lyons, Gregory M Woods
Devil facial tumour disease (DFTD) describes two genetically distinct transmissible tumours that pose a significant threat to the survival of the Tasmanian devil. A prophylactic vaccine could protect devils from DFTD transmission. For this vaccine to be effective, potent immune adjuvants will be required. Toll-like receptors (TLRs) promote robust immune responses in human cancer studies and are highly conserved across mammalian species. In this study, we investigated the proficiency of TLR ligands for immune activation in the Tasmanian devil using in vitro mononuclear cell stimulations and in vivo immunisation trials with a model antigen...
July 6, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28681506/safety-and-pharmacodynamics-of-intranasal-gsk2245035-a-tlr7-agonist-for-allergic-rhinitis-a-randomized-trial
#10
Anne K Ellis, Daphne C Tsitoura, Diana Quint, William Powley, Laurie A Lee
BACKGROUND: Toll-like receptor 7 (TLR7) stimulation in the airways may reduce responses to aeroallergens by induction of type 1 interferons (IFNs). GSK2245035 is a novel selective TLR7 agonist in pharmaceutical development. OBJECTIVE: Assessment of safety, pharmacodynamics and nasal allergic reactivity following repeated weekly intranasal (i.n.) GSK2245035. METHODS: This randomized, double-blind, placebo-controlled study (TL7116958) was conducted over two pollen seasons (2013-2014) and follow-up study (204509) conducted one year later...
July 5, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28676793/immune-responses-of-chickens-infected-with-wild-bird-origin-h5n6-avian-influenza-virus
#11
Shimin Gao, Yinfeng Kang, Runyu Yuan, Haili Ma, Bin Xiang, Zhaoxiong Wang, Xu Dai, Fumin Wang, Jiajie Xiao, Ming Liao, Tao Ren
Since April 2014, new infections of H5N6 avian influenza virus (AIV) in humans and domestic poultry have caused considerable economic losses in the poultry industry and posed an enormous threat to human health worldwide. In previous research using gene sequence and phylogenetic analysis, we reported that H5N6 AIV isolated in February 2015 (ZH283) in Pallas's sandgrouse was highly similar to that isolated in a human in December 2015 (A/Guangdong/ZQ874/2015), whereas a virus (i.e., SW8) isolated in oriental magpie-robin in 2014 was highly similar to that of A/chicken/Dongguan/2690/2013 (H5N6)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28671847/identification-and-optimization-of-pyrrolo-3-2-d-pyrimidine-toll-like-receptor-7-tlr7-selective-agonists-for-the-treatment-of-hepatitis-b
#12
David Craig McGowan, Florence Herschke, Frederik Pauwels, Bart Stoops, Ilham Smyej, Stefaan Last, Serge Pieters, Werner Embrechts, Mourad Daoubi Khamlichi, Tine Thoné, Bertrand Van Schoubroeck, Wendy Mostmans, Debbie Wuyts, Dorien Verstappen, Annick Scholliers, Dorien De Pooter, Deborah Dhuyvetter, Herman Borghys, Marianne Tuefferd, Eric Arnoult, Jin Hong, Gregory Fanning, Jacques Bollekens, Vijay Urmaliya, Ard Teisman, Helen Horton, Tim H M Jonckers, Pierre Jean Marie Bernard Raboisson
Pyrrolo[3,2-d]pyrimidines were identified as a new series of potent and selective TLR7 agonists. Compounds were optimized for their activity and selectivity over TLR8. This presents an advantage over recently described scaffolds that have residual TLR8 activity, which may be detrimental to the tolerability of the candidate drug. Oral administration of the lead compound 54 effectively induced a transient interferon stimulated gene (ISG) response in mice and cynomolgus monkeys. We aimed for a high first pass effect, limiting cytokine induction systemically, and demonstrated the potential for the immunotherapy of viral hepatitis...
July 3, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28665937/cholecalciferol-decreases-inflammation-and-improves-vitamin-d-regulatory-enzymes-in-lymphocytes-in-the-uremic-environment-a-randomized-controlled-pilot-trial
#13
José Tarcisio G Carvalho, Marion Schneider, Lilian Cuppari, Caren C Grabulosa, Danilo T Aoike, Beata Marie Q Redublo, Marcelo C Batista, Miguel Cendoroglo, Rosa Maria Moyses, Maria Aparecida Dalboni
It has been reported that vitamin D regulates the immune system. However, whether vitamin D repletion modulates inflammatory responses in lymphocytes from dialysis patients is unclear. In the clinical trial, thirty-two (32) dialysis patients with 25 vitamin D ≤ 20ng/mL were randomized to receive either supplementation of cholecalciferol 100,000 UI/week/3 months (16 patients) or placebo (16 patients). In the in vitro study, B and T lymphocytes from 12 healthy volunteers (HV) were incubated with or without uremic serum in the presence or absence of 25 or 1,25 vitamin D...
2017: PloS One
https://www.readbyqxmd.com/read/28665028/small-rnas-induce-the-activation-of-the-pro-inflammatory-tlr7-signaling-pathway-in-aged-rat-kidney
#14
Eun Kyeong Lee, Ki Wung Chung, Ye Ra Kim, Sugyeong Ha, Sung Dae Kim, Dae Hyun Kim, Kyung Jin Jung, Bonggi Lee, Eunok Im, Byung Pal Yu, Hae Young Chung
We have recently reported that TLR-related genes, including TLR7, are upregulated during aging. However, the role of TLR7 and its endogenous ligand in inflammation related to aging is not well defined. Here, we established that small RNAs trigger age-related renal inflammation via TLR7 signaling pathway. We first investigated the expression changes of nine different TLRs in kidney of 6-month-old young rats and 20-month-old aged rats. The results revealed that the expression of TLR7 was the highest among nine TLRs in kidney of old rats compared to the young aged rats...
June 30, 2017: Aging Cell
https://www.readbyqxmd.com/read/28655469/transcutaneous-immunization-with-a-novel-imiquimod-nanoemulsion-induces-superior-t-cell-responses-and-virus-protection
#15
Pamela Aranda Lopez, Mark Denny, Ann-Kathrin Hartmann, Astrid Alflen, Hans Christian Probst, Esther von Stebut, Stefan Tenzer, Hansjörg Schild, Michael Stassen, Peter Langguth, Markus P Radsak
BACKGROUND: Transcutaneous immunization (TCI) is a novel vaccination strategy utilizing the skin associated lymphatic tissue to induce immune responses. TCI using a cytotoxic T lymphocyte (CTL) epitope and the Toll-like receptor 7 (TLR7) agonist imiquimod mounts strong CTL responses by activation and maturation of skin-derived dendritic cells (DCs) and their migration to lymph nodes. However, TCI based on the commercial formulation Aldara only induces transient CTL responses that needs further improvement for the induction of durable therapeutic immune responses...
June 16, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28652534/poly-u-and-cpg-ameliorate-the-unbalanced-t-cell-immunity-and-pneumonia-of-mice-with-rsv-vaccine-enhanced-disease
#16
Ran Jia, Lu Lu, Xiaozhen Liang, Zhiwu Sun, Lingbing Tan, Menghua Xu, Liyun Su, Jin Xu
Respiratory Syncycial Virus (RSV) is the most important pathogen responsible for children's severe lower respiratory tract infection. So far no RSV vaccine has yet been authorized for clinical use. The main impediment that blocked development of RSV vaccine is that inactivated RSV vaccine could cause RSV vaccine-enhanced disease (RVED). The mechanism of RVED remains unclear. Recently some researchers found that insufficient activation of innate immunity, including Toll-like receptors (TLRs), might be associated with the onset of RVED...
June 26, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28652396/tlr7-signaling-regulates-th17-cells-and-autoimmunity-novel-potential-for-autoimmune-therapy
#17
Jian Ye, Yadan Wang, Xia Liu, Lingyun Li, Adeleye Opejin, Eddy C Hsueh, Huanle Luo, Tian Wang, Daniel Hawiger, Guangyong Peng
Innate regulation through TLR signaling has been shown to be important for promoting T cell subset development and function. However, limited information is known about whether differential TLR signaling can selectively inhibit Th17 and/or Th1 cells, which are important for controlling excessive inflammation and autoimmune responses. In this article, we demonstrate that activation of TLR7 signaling in T cells can inhibit Th17 cell differentiation from naive T cells and IL-17 production in established Th17 cells...
June 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28648870/tlr7-and-tlr8-agonist-resiquimod-r848-differently-regulates-mif-expression-in-cells-and-organs
#18
Yao Mawulikplimi Adzavon, Pengxiang Zhao, Baobei Lv, Mengyu Liu, Xin Zhang, Fei Xie, Linqi Yang, Lei Shang, Mingzi Zhang, Qinjian Li, Xuemei Ma
Since its first description in 1966, macrophage migration inhibitory factor (MIF) was found to play a critical role in inflammatory and immune responses as well as in disease pathogenesis especially in tumor pathogenesis and cancer progression. MIF is expressed in different cell types and is associated with many disease severity and tumor pathogenesis. Here, we investigated the influence of TLR7 and TLR8 agonist resiquimod (R848), an immune response inducer used as a prophylactic agent for several infectious diseases as well as anticancer agents and vaccine adjuvant on MIF expression in cells and organs...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28646802/dampness-can-promote-the-influenza-a-virus-and-worsen-its-prognosis-by-upregulating-the-tlr7-signaling-pathway
#19
Deng Li, Xu Huachong, Pang Peng, Zheng Ke, Nie Jiao, Wu Xianlin, Yu Bin, Chen Jia, Chen Xiaoyin
Context • Outbreaks of the influenza A virus (IAV) are increasingly recognized as a global public health issue, affecting a large proportion of the world's population. A number of studies have provided epidemiologic evidence that dampness and mold are consistently associated with multiple allergic and respiratory effects, but they focused on dampness-related pathogenic microorganisms leading to allergy rather than the dampness itself. Objective • The current study intended to examine the effects of a damp environment on the promotion of the IAV and determine the adverse effects on its prognosis through upregulation of the toll-like receptor 7 (TLR7)-signaling pathway in the lung...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28638786/polyelectrolyte-enrobed-cancer-cells-in-view-of-personalized-immune-therapy
#20
Lien Lybaert, Keun Ah Ryu, Riet De Rycke, Alfred C Chon, Olivier De Wever, Karim Y Vermaelen, Aaron Esser-Kahn, Bruno G De Geest
Targeting the immune system with a personalized vaccine containing cues derived from the patient's malignancy might be a promising approach in the fight against cancer. It includes neo-antigens as well as nonmutated tumor antigens, preferentially leading to an immune response that is directed to a broader range of epitopes compared to strategies involving a single antigen. Here, this paper reports on an elegant method to encapsulate whole cancer cells into polyelectrolyte particles. Porous and nonaggregated microparticles containing dead cancer cells are obtained by admixing mannitol and live cancer cells with oppositely charged polyelectrolytes, dextran sulfate (anionic polysaccharide), and poly-l-arginine (cationic polypeptide) prior to atomization into a hot air stream...
June 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
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