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https://www.readbyqxmd.com/read/29687651/tlr9-deficiency-breaks-tolerance-to-rna-associated-antigens-and-upregulates-tlr7-protein-in-sle1-mice
#1
Teja Celhar, Hiroko Yasuga, Hui-Yin Lee, Olga Zharkova, Shubhita Tripathi, Susannah I Thornhill, Hao K Lu, Bijin Au, Lina H K Lim, Thomas P Thamboo, Shizuo Akira, Edward K Wakeland, John E Connolly, Anna-Marie Fairhurst
OBJECTIVE: Toll-like receptors (TLRs) 7 and 9 are important innate signaling molecules with opposing roles in the development and progression of Systemic Lupus Erythematosus (SLE). While multiple studies support a dependency on TLR7 for disease development, genetic ablation of TLR9 results in severe disease with glomerulonephritis (GN) by a largely unknown mechanism. The present study was designed to examine the suppressive role of TLR9 in the development of severe lupus. METHODS: We crossed Sle1 lupus-prone mice with TLR9-deficient mice to generate Sle1TLR9-/- ...
April 24, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29686670/alum-toll-like-receptor-7-adjuvant-enhances-the-expansion-of-memory-b-cell-compartment-within-the-draining-lymph-node
#2
Hoa Thi My Vo, Barbara Christiane Baudner, Stefano Sammicheli, Matteo Iannacone, Ugo D'Oro, Diego Piccioli
Vaccination is one of the most cost-effective health interventions and, with the exception of water sanitization, no other action has had such a major effect in mortality reduction. Combined with other approaches, such as clean water, better hygiene, and health education, vaccination contributed to prevent millions of cases of deaths among children under 5 years of age. New or improved vaccines are needed to fight some vaccine-preventable diseases that are still a threat for the public health globally, as reported also in the Global Vaccine Action Plan (GVAP) endorsed by the World Health Assembly in 2012...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29678225/synergistic-effect-of-co-stimulation-of-membrane-and-endosomal-tlrs-on-chicken-innate-immune-responses
#3
Sungwon Kim, Pete Kaiser, Dominika Borowska, Lonneke Vervelde
Toll-like receptor (TLR) ligands (TLR-Ls) are critical activators of immunity and are successfully being developed as vaccine adjuvants in both mammals and birds. In this study, we investigated the synergistic effect of co-stimulation of membrane and endosomal TLRs on the innate immune responses using chicken bone marrow-derived macrophages (BMMs), and studied the effect of age on the induction of innate responses. BMMs from 1 and 4-week-old birds were stimulated with Pam3Cys-SK4 (PCSK; TLR2), synthetic monophosphoryl lipid A (MPLA), Di[3-deoxy-d-manno-octulosonyl]-lipid A ammonium salt (KLA; TLR4), Gardiquimod, Resiquimod (R848; TLR7), CpG class B and C (TLR21)...
May 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29673738/tbk1-a-key-regulator-and-potential-treatment-target-for-interferon-positive-sj%C3%A3-gren-s-syndrome-systemic-lupus-erythematosus-and-systemic-sclerosis
#4
Iris L A Bodewes, Erika Huijser, Cornelia G van Helden-Meeuwsen, Liselotte Tas, Ruth Huizinga, Virgil A S H Dalm, P Martin van Hagen, Noortje Groot, Sylvia Kamphuis, Paul L A van Daele, Marjan A Versnel
OBJECTIVE: Upregulation of type I interferons (IFN-I) is a hallmark of systemic autoimmune diseases like primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Expression of IFN-I is induced by three different receptor families: Toll-like receptors (TLRs), RIG-like receptors (RLRs) and DNA-sensing receptors (DSRs). TANK-binding kinase (TBK1) is an important signaling hub downstream of RLRs and DSRs. TBK1 activates IRF3 and IRF7, leading to IFN-I production and subsequent induction of interferon stimulated genes (ISGs)...
April 16, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29673285/tlr-agonist-combinations-that-stimulate-th-type-i-polarizing-responses-from-human-neonates
#5
Naveen Surendran, Andrea Simmons, Michael E Pichichero
Each year millions of neonates die due to vaccine preventable infectious diseases. Our study seeks to develop novel neonatal vaccines and improve immunogenicity of early childhood vaccines by incorporating TLR agonist-adjuvant combinations that overcome the inherent neonatal Th2 bias and stimulate Th1 polarizing response from neonatal APCs. We systematically stimulated cord blood mononuclear cells with single and multiple combinations of TLR agonists and measured levels of IL-12p70, IFN-γ, IFN-α, IL-10, IL-13, TNF-α, IL-6 and IL-1β from cell culture supernatants...
January 1, 2018: Innate Immunity
https://www.readbyqxmd.com/read/29670923/cathelicidin-ll-37-affects-surface-and-intracellular-toll-like-receptor-expression-in-tissue-mast-cells
#6
Justyna Agier, Ewa Brzezińska-Błaszczyk, Paulina Żelechowska, Magdalena Wiktorska, Jacek Pietrzak, Sylwia Różalska
Undoubtedly, mast cells take part in host defense against microorganisms as they are numerous at the portal of infection, they release many proinflammatory and antimicrobial mediators, and they express pattern recognition receptors, such as TLRs. These receptors play a key role in recognition and binding molecules associated with microorganisms and molecules associated with damage. Cathelicidins exhibit direct antimicrobial activities against a broad spectrum of microbes by perturbing their cell membranes. Accumulating evidence suggests a role for these molecules in supporting cell activation...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29670609/enhanced-replication-of-virulent-newcastle-disease-virus-in-chicken-macrophages-is-due-to-polarized-activation-of-cells-by-inhibition-of-tlr7
#7
Pingze Zhang, Zhuang Ding, Xinxin Liu, Yanyu Chen, Junjiao Li, Zhi Tao, Yidong Fei, Cong Xue, Jing Qian, Xueli Wang, Qingmei Li, Tobias Stoeger, Jianjun Chen, Yuhai Bi, Renfu Yin
Newcastle disease (ND), caused by infections with virulent strains of Newcastle disease virus (NDV), is one of the most important infectious disease affecting wild, peridomestic, and domestic birds worldwide. Vaccines constructed from live, low-virulence (lentogenic) viruses are the most accepted prevention and control strategies for combating ND in poultry across the globe. Avian macrophages are one of the first cell lines of defense against microbial infection, responding to signals in the microenvironment...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29669251/self-renewal-and-toll-like-receptor-signaling-sustain-exhausted-plasmacytoid-dendritic-cells-during-chronic-viral-infection
#8
Monica Macal, Yeara Jo, Simone Dallari, Aaron Y Chang, Jihong Dai, Shobha Swaminathan, Ellen J Wehrens, Patricia Fitzgerald-Bocarsly, Elina I Zúñiga
Although characterization of T cell exhaustion has unlocked powerful immunotherapies, the mechanisms sustaining adaptations of short-lived innate cells to chronic inflammatory settings remain unknown. During murine chronic viral infection, we found that concerted events in bone marrow and spleen mediated by type I interferon (IFN-I) and Toll-like receptor 7 (TLR7) maintained a pool of functionally exhausted plasmacytoid dendritic cells (pDCs). In the bone marrow, IFN-I compromised the number and the developmental capacity of pDC progenitors, which generated dysfunctional pDCs...
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29667229/uc-1v150-a-potent-tlr7-agonist-capable-of-activating-macrophages-and-potentiating-mab-mediated-target-cell-deletion
#9
Lekh N Dahal, Adam Gadd, Alexander D Edwards, Mark S Cragg, Stephen A Beers
Toll like receptors (TLR) are critical mediators of the immune system with their activation linked to infection, inflammation and the pathogenesis of immune diseases including autoimmunity and cancer. For this reason, over the last two decades, TLR and their associated signalling pathways have been targeted therapeutically to enhance innate and adaptive immunity. Several TLR ligands, both endogenous and synthetic are at various phases of clinical testing, and new ligands are continually emerging. Agonists of TLR7 are known immune response modifiers, simultaneously stimulating several cell types, resulting in immune cell activation and cytokine and chemokine release...
April 18, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29665497/the-effects-of-resiquimod-in-an-ovalbumin-induced-allergic-rhinitis-model
#10
Shenhong Qu, Taijie Qin, Min Li, Shaojie Zhang, Linsong Ye, Jiazhang Wei, Hua Fan, Baiwen Chen
Growing evidence indicates that the Toll-like receptor7/8(TLR7/8) agonist resiquimod (R848) is a potential inhibitor of type-2 immunity. However, the mechanisms mediating its therapeutic effects are not fully understood. This study investigated the effects of R848 on OVA-induced allergic rhinitis(AR) mice and the expression of IL-25, IL-33, TSLP, T-cell immunoglobulin mucin1 (TIM1) and T-cell immunoglobulin mucin3 (TIM3). BALB/c mice were intranasally sensitized and challenged with ovalbumin (OVA), and R848 was intraperitoneally injected into AR mice...
April 14, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29662819/variable-localization-of-toll-like-receptors-in-human-fallopian-tube-epithelial-cells
#11
Fatemehsadat Amjadi, Zahra Zandieh, Ensieh Salehi, Reza Jafari, Nasrin Ghasemi, Abbas Aflatoonian, Alireza Fazeli, Reza Aflatoonian
Objective: To determine the localization, expression, and function of Toll-like receptors (TLRs) in fallopian tube epithelial cells. Methods: The localization of TLRs in fallopian tube epithelial cells was investigated by immunostaining. Surprisingly, the intensity of staining was not equal in the secretory and ciliated cells. After primary cell culture of fallopian tube epithelial cells, ring cloning was used to isolate colonies of ciliated epithelial cells, distinct from non-ciliated epithelial cells...
March 2018: Clinical and Experimental Reproductive Medicine
https://www.readbyqxmd.com/read/29656235/effective-cancer-immunotherapy-in-mice-by-polyic-imiquimod-complexes-and-engineered-magnetic-nanoparticles
#12
Ana Isabel Bocanegra Gondan, Ane Ruiz-de-Angulo, Aintzane Zabaleta, Nina Gómez Blanco, Beatriz Macarena Cobaleda-Siles, María Jesús García-Granda, Daniel Padro, Jordi Llop, Blanca Arnaiz, María Gato, David Escors, Juan C Mareque-Rivas
Encouraging results are emerging from systems that exploit Toll like receptor (TLR) signaling, nanotechnology, checkpoint inhibition and molecular imaging for cancer immunotherapy. A major remaining challenge is developing effective, durable and tumour-specific immune responses without systemic toxicity. Here, we report a simple and versatile system based on synergistic activation of immune responses and direct cancer cell killing by combined TLR ligation using polyIC as TLR3 and imiquimod (R837) as TLR7 agonist, in combination with the model antigen ovalbumin (OVA) and phospholipid micelles loaded with zinc-doped iron oxide magnetic nanoparticles (MNPs)...
April 3, 2018: Biomaterials
https://www.readbyqxmd.com/read/29644700/snp-based-susceptibility-resistance-association-and-mrna-expression-regulation-analyses-of-tlr7-to-grass-carp-ctenopharyngodon-idella-reovirus
#13
J J Su, X Y Shang, Q Y Wan, J G Su
Eleven single nucleotide polymorphisms (SNP) in Ctenopharyngodon idella toll-like receptor 7 (citlr7) gene, containing two in the 5'-flanking region, three within the single intron and six distributed in the coding sequence (CDS), were identified. A case-control study of 73 susceptible individuals and 67 resistant individuals was conducted to test the SNPs-based susceptibility-resistance association and mRNA expression of citlr7 to grass carp reovirus (GCRV), showing that both 820 A/G and 1726 A/G were significantly correlative sites in genotype (P < 0·05)...
April 11, 2018: Journal of Fish Biology
https://www.readbyqxmd.com/read/29625894/toll-like-receptor-9-contains-two-dna-binding-sites-that-function-cooperatively-to-promote-receptor-dimerization-and-activation
#14
Umeharu Ohto, Hanako Ishida, Takuma Shibata, Ryota Sato, Kensuke Miyake, Toshiyuki Shimizu
Toll-like receptor 9 (TLR9) recognizes DNA containing CpG motifs derived from bacteria and viruses and activates the innate immune response to eliminate them. TLR9 is known to bind to CpG DNA, and here, we identified another DNA binding site in TLR9 that binds DNA containing cytosine at the second position from the 5' end (5'-xCx DNA). 5'-xCx DNAs bound to TLR9 in the presence of CpG DNA and cooperatively promoted dimerization and activation of TLR9. Binding at both sites was important for efficient activation of TLR9...
March 24, 2018: Immunity
https://www.readbyqxmd.com/read/29618665/b-lymphocytes-confer-immune-tolerance-via-cell-surface-garp-tgf-%C3%AE-complex
#15
Caroline H Wallace, Bill X Wu, Mohammad Salem, Ephraim A Ansa-Addo, Alessandra Metelli, Shaoli Sun, Gary Gilkeson, Mark J Shlomchik, Bei Liu, Zihai Li
GARP, a cell surface docking receptor for binding and activating latent TGF-β, is highly expressed by platelets and activated Tregs. While GARP is implicated in immune invasion in cancer, the roles of the GARP-TGF-β axis in systemic autoimmune diseases are unknown. Although B cells do not express GARP at baseline, we found that the GARP-TGF-β complex is induced on activated human and mouse B cells by ligands for multiple TLRs, including TLR4, TLR7, and TLR9. GARP overexpression on B cells inhibited their proliferation, induced IgA class-switching, and dampened T cell-independent antibody production...
April 5, 2018: JCI Insight
https://www.readbyqxmd.com/read/29611821/galectin-9-inhibits-tlr7-mediated-autoimmunity-in-murine-lupus-models
#16
Santosh K Panda, Valeria Facchinetti, Elisaveta Voynova, Shino Hanabuchi, Jodi L Karnell, Richard N Hanna, Roland Kolbeck, Miguel A Sanjuan, Rachel Ettinger, Yong-Jun Liu
Uncontrolled secretion of type I IFN, as the result of endosomal TLR (i.e., TLR7 and TLR9) signaling in plasmacytoid DCs (pDCs), and abnormal production of autoantibodies by B cells are critical for systemic lupus erythematosus (SLE) pathogenesis. The importance of galectin-9 (Gal-9) in regulating various autoimmune diseases, including lupus, has been demonstrated. However, the precise mechanism by which Gal-9 mediates this effect remains unclear. Here, using spontaneous murine models of lupus (i.e., BXSB/MpJ and NZB/W F1 mice), we demonstrate that administration of Gal-9 results in reduced TLR7-mediated autoimmune manifestations...
April 3, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29608601/sting-agonists-enable-antiviral-cross-talk-between-human-cells-and-confer-protection-against-genital-herpes-in-mice
#17
Morten K Skouboe, Alice Knudsen, Line S Reinert, Cedric Boularan, Thierry Lioux, Eric Perouzel, Martin K Thomsen, Søren R Paludan
In recent years, there has been an increasing interest in immunomodulatory therapy as a means to treat various conditions, including infectious diseases. For instance, Toll-like receptor (TLR) agonists have been evaluated for treatment of genital herpes. However, although the TLR7 agonist imiquimod was shown to have antiviral activity in individual patients, no significant effects were observed in clinical trials, and the compound also exhibited significant side effects, including local inflammation. Cytosolic DNA is detected by the enzyme cyclic GMP-AMP (2'3'-cGAMP) synthase (cGAS) to stimulate antiviral pathways, mainly through induction of type I interferon (IFN)s...
April 2, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29600623/-effect-and-mechanism-of-mahuang-tang-against-influenza-a-h1n1-virus-in-vitro
#18
Wen-Yang Wei, Hai-Tong Wan, Li Yu, Yi-Yu Lu, Yu He
To study the effect and underlying mechanism of Mahuang Tang against influenza A virus in vitro , the influenza virus-infected Madin-Darby canine kidney(MDCK) cells were used as the carrier in this study to detect the median tissue culture-infective dose(TCID₅₀) of influenza A virus strains(A/PR8/34) on MDCK cells with cytopathic effect(CPE) assay. Blocking influenza virus invading host cells and anti-influenza virus biosynthesis were used as two different administration methods, and then the methyl thiazolyl tetrazolium(MTT) assay was utilized to determine the antiviral effective rate(ER), median efficacious concentration(EC₅₀) and therapeutic index(TI) of Mahuang Tang...
February 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29599669/x-linked-tlr7-gene-polymorphisms-are-associated-with-diverse-immunological-conditions-but-not-with-discoid-lupus-erythematosus-in-polish-patients
#19
Katarzyna Skonieczna, Anna Woźniacka, Rafał Czajkowski, Jan Styczyński, Anna Krenska, Ewa Robak, Mariusz Gawrych, Sebastian Kaszewski, Mariusz Wysocki, Tomasz Grzybowski
Introduction: Toll-like receptor 7 (TLR7) is an important molecule involved in the development of autoimmunity and the response to different pathogens. Several polymorphisms within the TLR7 gene were previously found to be associated with systemic lupus erythematosus (SLE). However, none of those studies investigated the TLR7 promoter flanking variants rs1634318 and rs1616583. TLR7 gene diversity has not been analyzed with respect to discoid lupus erythematosus (DLE) development, while its role in the human immunological response to fungal infection is not fully known...
February 2018: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/29593047/il-27r-signalling-mediates-early-viral-containment-and-impacts-innate-and-adaptive-immunity-after-chronic-lymphocytic-choriomeningitis-virus-infection
#20
James A Harker, Kurt A Wong, Simone Dallari, Phuc Bao, Aleksandr Dolgoter, Yeara Jo, Ellen J Wehrens, Monica Macal, Elina I Zuniga
Chronic viral infections represent a major challenge to host's immune response and a unique network of immunological elements, including cytokines, are required for their containment. By using a model persistent infection with the natural murine pathogen lymphocytic choriomeningitis virus clone 13 (LCMV Cl13) we investigated the role of one such cytokine, interleukin 27 (IL-27), in the control of chronic infection. We found that IL-27R signalling promoted control of LCMV Cl13 as early as day 1 and 5 after infection and that il27p28 transcripts were rapidly elevated in multiple subsets of dendritic cells (DCs) and myeloid cells...
March 28, 2018: Journal of Virology
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