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https://www.readbyqxmd.com/read/27916934/immune-related-gene-expression-patterns-in-gpv-or-h9n2-infected-goose-spleens
#1
Shun Chen, Anqi Wang, Lipei Sun, Fei Liu, Mingshu Wang, Renyong Jia, Dekang Zhu, Mafeng Liu, Qiao Yang, Ying Wu, Kunfeng Sun, Xiaoyue Chen, Anchun Cheng
Goose parvovirus (GPV) and avian influenza virus subtype H9N2 are single-stranded DNA (ssDNA) and single-stranded RNA (ssRNA) viruses, respectively, both of which can spread in goslings and cause a significant economic loss. To explore the comprehensive transcriptome of GPV- or H9N2-infected goose spleens and to understand the immune responses induced by a DNA virus (GPV) or a RNA virus (H9N2), RNA-seq was performed on the spleens of goslings at the fifth day post infection. In the present study, 2604 and 2409 differentially expressed unigenes were identified in the GPV- and H9N2-infected groups, respectively...
December 1, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27905985/tlr7-8-agonist-induces-a-post-entry-samhd1-independent-block-to-hiv-1-infection-of-monocytes
#2
Henning Hofmann, Bénédicte Vanwalscappel, Nicolin Bloch, Nathaniel R Landau
BACKGROUND: Monocytes, the primary myeloid cell-type in peripheral blood, are resistant to HIV-1 infection as a result of the lentiviral restriction factor SAMHD1. Toll-like receptors recognize microbial pathogen components, inducing the expression of antiviral host proteins and proinflammatory cytokines. TLR agonists that mimic microbial ligands have been found to have activity against HIV-1 in macrophages. The induction of restriction factors in monocytes by TLR agonist activation has not been well studied...
December 1, 2016: Retrovirology
https://www.readbyqxmd.com/read/27902922/the-extent-to-which-immunity-apoptosis-and-detoxification-gene-expression-interact-with-17-alpha-methyltestosterone
#3
Haitham G Abo-Al-Ela, Abeer F El-Nahas, Shawky Mahmoud, Essam M Ibrahim
Innate immunity is the first line of defence against invasion by foreign pathogens. One widely used synthetic androgen for the production of all-male fish, particularly commercially valuable Nile tilapia, Oreochromis niloticus, is 17 alpha-methyltestosterone (MT). The present study investigates the effect of MT on innate immunity, cellular apoptosis and detoxification and the mortality rate, during and after the feeding of fry with 0-, 40-and 60-mg MT/kg. Expression analysis was completed on interleukin 1 beta (il1β), interleukin 8 (il8), tumour necrosis factor alpha (tnfα), CXC2- and CC-chemokines, interferon (ifn), myxovirus resistance (mx), toll-like receptor 7 (tlr7), immunoglobulin M heavy chain (IgM heavy chain), vitellogenin (vtg), cellular apoptosis susceptibility (cas) and glutathione S-transferase α1 (gstα1)...
November 27, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27891600/human-pdcs-display-sex-specific-differences-in-type-i-interferon-subtypes-and-interferon-%C3%AE-%C3%AE-receptor-expression
#4
Susanne Ziegler, Claudia Beisel, Kathrin Sutter, Morgane Griesbeck, Heike Hildebrandt, Sven Hagen, Ulf Dittmer, Marcus Altfeld
The outcomes of many diseases differ between women and men, with women experiencing a higher incidence and more severe pathogenesis of autoimmune and some infectious diseases. It has been suggested that this is partially due to activation of plasmacytoid dendritic cells (pDCs), the main producers of interferon (IFN)-α, in response to toll-like receptor (TLR) 7 stimulation. We investigated the induction of type I IFN (IFN-I) subtypes upon TLR7 stimulation on isolated pDCs. Our data revealed a sex-specific differential expression of IFN-Is, with pDCs from females showing a significantly higher mRNA expression of all 13 IFNα-subtypes...
November 28, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27891130/molecular-mechanisms-that-underlie-the-dynamic-adaptation-of-innate-monocyte-memory-to-varying-stimulant-strength-of-tlr-ligands
#5
Ruoxi Yuan, Shuo Geng, Liwu Li
In adaptation to rising stimulant strength, innate monocytes can be dynamically programed to preferentially express either pro- or anti-inflammatory mediators. Such dynamic innate adaptation or programing may bear profound relevance in host health and disease. However, molecular mechanisms that govern innate adaptation to varying strength of stimulants are not well understood. Using lipopolysaccharide (LPS), the model stimulant of toll-like-receptor 4 (TLR4), we reported that the expressions of pro-inflammatory mediators are preferentially sustained in monocytes adapted by lower doses of LPS, and suppressed/tolerized in monocytes adapted by higher doses of LPS...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27890931/a-tlr7-agonist-enhances-the-anti-tumor-efficacy-of-obinutuzumab-in-murine-lymphoma-models-via-nk-cells-and-cd4-t-cells
#6
E J Cheadle, G Lipowska-Bhalla, S J Dovedi, E Fagnano, C Klein, J Honeychurch, T M Illidge
Anti-CD20 mAb such as rituximab have proven highly effective at improving outcome in B-cell malignancies. However, many patients ultimately relapse and become refractory to treatment. The glycoengineered anti-CD20 mAb obinutuzumab was developed to induce enhanced antibody dependent cellular cytotoxicity, antibody dependent phagocytosis and direct cell death and was shown to lead to improved outcomes in a randomized study in B-chronic lymphocytic leukemia (B-CLL). We hypothesized that immune stimulation through TLR7 agonism in combination with obinutuzumab would further enhance lymphoma clearance and the generation of long-term anti-tumor immune responses...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27880772/t-cell-production-of-ifn%C3%AE-in-response-to-tlr7-il-12-stimulates-optimal-b-cell-responses-to-viruses
#7
Kira Rubtsova, Anatoly V Rubtsov, Kalani Halemano, Sam X Li, John W Kappler, Mario L Santiago, Philippa Marrack
Knowledge of the processes that underlie IgG subclass switching could inform strategies designed to counteract infections and autoimmunity. Here we show that TLR7 ligands induce subsets of memory CD4 and CD8 T cells to secrete interferon γ (IFNγ) in the absence of antigen receptor stimulation. In turn, TLR ligation and IFNγ cause B cells to express the transcription factor, T-bet, and to switch immunoglobulin production to IgG2a/c. Absence of TLR7 in T cells leads to the impaired T-bet expression in B cells and subsequent inefficient IgG2a isotype switching both in vitro and during the infection with Friend virus in vivo...
2016: PloS One
https://www.readbyqxmd.com/read/27876497/hepatitis-c-virus-inhibits-cd4-t-cell-function-via-binding-to-toll-like-receptor-7
#8
Dalila Mele, Stefania Mantovani, Barbara Oliviero, Giulia Grossi, Serena Ludovisi, Mario U Mondelli, Stefania Varchetta
Toll-like receptor 7 (TLR7) is a ssRNA receptor that activates dendritic cells and macrophages upon ssRNA binding; however, little is known of its role in CD4(+) T cells. We show here that hepatitis C virus (HCV) induces a dose dependent inhibition of cytokine production and expression of activation markers in CD4 T cells, which were restored by a TLR7-specific antagonist. These findings indicate that HCV induces CD4 T cell impairment via TLR7 which may contribute to failure of virus eradication, casting doubts on the use of TLR7 agonists to boost innate immunity in chronic RNA virus infections...
November 19, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27864474/complement-component-3-regulates-ifn-%C3%AE-production-by-plasmacytoid-dendritic-cells-following-tlr7-activation-by-a-plant-virus-like-nanoparticle
#9
Marie-Ève Lebel, Marie-Pierre Langlois, Jean-François Daudelin, Esther Tarrab, Pierre Savard, Denis Leclerc, Alain Lamarre
The increasing use of plant viruses for the development of new vaccines and immunotherapy approaches poses questions regarding the mechanism by which the mammalian immune system recognizes these viruses. For example, although natural Abs (NA) and complement are key components of the innate immune system involved in the opsonization, phagocytosis, and destruction of microorganisms infecting mammals, their implication in plant virus recognition and immunogenicity is not well defined. In this study, we address the involvement of NA and the complement system in the activation of innate immunity through engagement of TLR7 with papaya mosaic virus (PapMV)-like nanoparticles...
November 18, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27864310/low-tlr7-gene-expression-in-atherosclerotic-plaques-is-associated-with-major-adverse-cardio-and-cerebrovascular-events
#10
Glykeria Karadimou, Lasse Folkersen, Martin Berg, Ljubica Perisic, Andrea Discacciati, Joy Roy, Göran K Hansson, Jonas Persson, Gabrielle Paulsson-Berne
AIMS: Processes in the development of atherosclerotic lesions can lead to plaque rupture or erosion, which can in turn elicit myocardial infarction or ischaemic stroke. The aims of this study were to determine whether Toll-like receptor 7 (TLR7) gene expression levels influence patient outcome and to explore the mechanisms linked to TLR7 expression in atherosclerosis. METHODS AND RESULTS: Atherosclerotic plaques were removed by carotid endarterectomy (CEA) and subjected to gene array expression analysis (n=123)...
November 15, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27852323/circulating-exosomes-from-patients-with-systemic-lupus-erythematosus-induce-an-proinflammatory-immune-response
#11
Joo Youn Lee, Jin Kyun Park, Eun Young Lee, Eun Bong Lee, Yeong Wook Song
BACKGROUND: Exosomes are involved in intercellular communication. The aim of this study was to investigate whether circulating exosomes effectively contribute to the inflammatory response in systemic lupus erythematosus (SLE). METHODS: Exosomes were purified from SLE patients and healthy controls (HCs). Healthy peripheral blood mononuclear cells (PBMCs) were stimulated with exosomes isolated from SLE patients and HCs in the presence or absence of Toll-like receptor (TLR) inhibitors...
November 16, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27847326/adsorption-of-a-synthetic-tlr7-8-ligand-to-aluminum-oxyhydroxide-for-enhanced-vaccine-adjuvant-activity-a-formulation-approach
#12
Christopher B Fox, Mark T Orr, Neal Van Hoeven, Sarah C Parker, Traci J T Mikasa, Tony Phan, Elyse A Beebe, Ghislain I Nana, Sharvari W Joshi, Mark A Tomai, James Elvecrog, Timothy R Fouts, Steven G Reed
For nearly a century, aluminum salts have been the most widely used vaccine adjuvant formulation, and have thus established a history of safety and efficacy. Nevertheless, for extremely challenging disease targets such as tuberculosis or HIV, the adjuvant activity of aluminum salts may not be potent enough to achieve protective efficacy. Adsorption of TLR ligands to aluminum salts facilitates enhanced adjuvant activity, such as in the human papilloma virus vaccine Cervarix®. However, some TLR ligands such as TLR7/8 agonist imidazoquinolines do not efficiently adsorb to aluminum salts...
November 12, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27832963/gotlr7-but-not-gotlr21-mediated-antiviral-immune-responses-against-low-pathogenic-h9n2-aiv-and-newcastle-disease-virus-infection
#13
Bing Yan, Jinyue Zhang, Wei Zhang, Mingshu Wang, Renyong Jia, Dekang Zhu, Mafeng Liu, Qiao Yang, Ying Wu, Kunfeng Sun, Xiaoyue Chen, Anchun Cheng, Shun Chen
Aquatic birds are considered the biological and genetic reservoirs of avian influenza virus and play a critical role in the transmission and dissemination of Newcastle Disease Virus (NDV). Both TLR7 and TLR21 are important for the host antiviral immune response. In an in vivo study, goTLR7, not goTLR21, was significantly up-regulated in the lungs of geese at 3 to 7 d after challenge with H9N2. And goOASL expression was induced in the bursa of fabricius, harderian glands and lungs. An increase in goRIG-I was detected in the lung and small intestine, whereas goPKR was increased in the lung but decreased in the thymus...
November 8, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27829595/imiquimod-induced-ccr9-ameliorates-murine-tnbs-colitis
#14
Ryoma Suzuki, Kyoko Katakura, Tatsuo Fujiwara, Naohiko Gunji, Hiroshi Watanabe, Hiromasa Ohira
To investigate whether Imiquimod (IMQ) as TLR7 ligand protects mice from colonic inflammation and the mechanisms underlying in such immunoregulatory conditions. METHODS: Murine colitis was induced to Balb/c mice by administration of trinitrobenzene sulfonic acid (TNBS) with or without daily intraperitoneal administration of IMQ. Colitis was evaluated by body weight decreases and by histological score. Also colonic mRNA expression was measured by RT-PCR. To confirm the induction of Regulatory T cells (Tregs) by type-1 IFN from pDCs, we generated mouse bone marrow-derived pDCs and co-cultured these with CD4(+) T cells isolated from mouse spleen with or without IMQ stimulation...
November 10, 2016: Fukushima Journal of Medical Science
https://www.readbyqxmd.com/read/27825468/novel-therapeutic-targets-in-waldenstrom-macroglobulinemia
#15
REVIEW
Aneel Paulus, Sikander Ailawadhi, Asher Chanan-Khan
Understanding of molecular mechanisms that drive Waldenstrom macroglobulinemia (WM) cell survival are rapidly evolving. This review briefly highlights emerging "WM-relevant" targets; for which therapeutic strategies are currently being investigated in preclinical and clinical studies. With the discovery of MYD88L265P signaling and remarkable activity of ibrutinib in WM, other targets within the B-cell receptor pathway are now being focused on for therapeutic intervention. Additional targets which play a role in WM cell survival include TLR7, 8 and 9, proteasome-associated deubiquitinating enzymes (USP14 and UCHL5), XPO1/CRM1 and AURKA...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27820700/the-transcription-factor-nr4a3-controls-cd103-dendritic-cell-migration
#16
Kiwon Park, Zbigniew Mikulski, Goo-Young Seo, Aleksander Y Andreyev, Paola Marcovecchio, Amy Blatchley, Mitchell Kronenberg, Catherine C Hedrick
The transcription factor NR4A3 (also known as NOR-1) is a member of the Nr4a family of nuclear receptors and is expressed in myeloid and lymphoid cells. Here, we have shown that Nr4a3 is essential for the migration of CD103+ dendritic cells (DCs) to lymph nodes (LNs). Nr4a3-deficient mice had very few CD103+ migratory DCs (mDCs) present in LNs, and mixed-chimera studies revealed that this migratory defect was cell intrinsic. We further found that CD103+ DCs from Nr4a3-deficient mice displayed a marked loss of surface expression of the chemokine CCR7...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27818460/different-expression-patterns-of-toll-like-receptor-mrnas-in-blood-mononuclear-cells-of-iga-nephropathy-and-iga-vasculitis-with-nephritis
#17
Ayano Saito, Atsushi Komatsuda, Hajime Kaga, Ryuta Sato, Masaru Togashi, Shin Okuyama, Hideki Wakui, Naoto Takahashi
Mucosal immunity may play a key role in IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAVN). IgAVN is characterized by the presence of non-thrombocytopenic palpable purpura, associated with glomerulonephritis with IgA-dominant immune deposits. Recent studies have shown the up-regulation of Toll-like receptors (TLRs) in patients with IgAN or IgAVN. Among TLRs that mediate innate immune reactions, TLR2, TLR4, and TRL5 recognize bacterial components, while TLR3, TLR7, and TLR9 recognize viral components...
2016: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27810925/cd72-negatively-regulates-b-lymphocyte-responses-to-the-lupus-related-endogenous-toll-like-receptor-7-ligand-sm-rnp
#18
Chizuru Akatsu, Kenro Shinagawa, Nobutaka Numoto, Zhihong Liu, Ayse Konuskan Ucar, Mohammad Aslam, Shirly Phoon, Takahiro Adachi, Koji Furukawa, Nobutoshi Ito, Takeshi Tsubata
Toll-like receptor 7 (TLR7) plays an essential role in development of systemic lupus erythematosus by co-stimulating B cells reactive to the endogenous TLR7 ligand Sm/ribonucleoprotein (RNP), a crucial lupus self-antigen. However, how the TLR7-mediated autoimmune response is regulated is not yet known. In this study, we demonstrate that CD72, an inhibitory B cell co-receptor known to prevent development of lupus, recognizes Sm/RNP at the extracellular C-type lectin-like domain (CTLD) and specifically inhibits B cell response to Sm/RNP...
November 14, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27807192/suppression-of-irak1-or-irak4-catalytic-activity-but-not-type-1-ifn-signaling-prevents-lupus-nephritis-in-mice-expressing-a-ubiquitin-binding-defective-mutant-of-abin1
#19
Sambit K Nanda, Marta Lopez-Pelaez, J Simon C Arthur, Francesco Marchesi, Philip Cohen
Polymorphisms in the TNIP1 gene encoding A20-binding inhibitor of NF-κB1 (ABIN1) predispose to lupus and other autoimmune diseases in at least eight human populations. We found previously that knock-in mice expressing a ubiquitin-binding-defective mutant of ABIN1 (ABIN1[D485N]) develop autoimmunity as they age and succumb to a disease resembling lupus nephritis in humans. In this article, we report that Flt3-derived dendritic cells from these mice overproduced type 1 IFNs upon stimulation with ligands that activate TLR7 or TLR9...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27799314/il-27-is-essential-for-suppression-of-experimental-allergic-asthma-by-the-tlr7-8-agonist-r848-resiquimod
#20
Adan Chari Jirmo, Kathleen Daluege, Christine Happle, Melanie Albrecht, Anna-Maria Dittrich, Mandy Busse, Anika Habener, Jelena Skuljec, Gesine Hansen
Different models of experimental allergic asthma have shown that the TLR7/8 agonist resiquimod (R848) is a potential inhibitor of type 2 helper cell-driven inflammatory responses. However, the mechanisms mediating its therapeutic effects are not fully understood. Using a model of experimental allergic asthma, we show that induction of IL-27 by R848 is critical for the observed ameliorative effects. R848 significantly inhibited all hallmarks of experimental allergic asthma, including airway hyperreactivity, eosinophilic airway inflammation, mucus hypersecretion, and Ag-specific Ig production...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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