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https://www.readbyqxmd.com/read/27922679/repetitive-extragenic-palindromic-dna-sequences-from-brucella%C3%A2-melitensis-stimulate-toll-like-receptor-9-signaling-in-macrophages
#1
Hui Yu, Liyun Bai, Yaxian Zhang, Zhanli Wang, Yongchun Yu
Brucella DNA activates the host innate immune system via the intracellular Toll-like receptor 9 (TLR9). However, the Brucella DNA sequences which are responsible for these immunostimulatory effects remain to be elucidated. The present study demonstrated that repetitive extragenic palindromic (REPs) sequences present in Brucella DNA were able to stimulate macrophages through TLR9. The induction of interferon-α (IFN-α) production by Brucella REPs was detected in cultured RAW264.7 mouse macrophages as well as in Wistar rats...
December 6, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27920152/toll-like-receptor-9-stimulation-induces-aberrant-expression-of-a-proliferation-inducing-ligand-by-tonsillar-germinal-center-b-cells-in-iga-nephropathy
#2
Masahiro Muto, Benoit Manfroi, Hitoshi Suzuki, Kensuke Joh, Masaaki Nagai, Sachiko Wakai, Christian Righini, Masayuki Maiguma, Shozo Izui, Yasuhiko Tomino, Bertrand Huard, Yusuke Suzuki
The TNF family member a proliferation-inducing ligand (APRIL; also known as TNFSF13), produced by myeloid cells, participates in the generation and survival of antibody-producing plasma cells. We studied the potential role of APRIL in the pathogenesis of IgA nephropathy (IgAN). We found that a significant proportion of germinal centers (GCs) in tonsils of patients with IgAN contained cells aberrantly producing APRIL, contributing to an overall upregulation of tonsillar APRIL expression compared with that in tonsils of control patients with tonsillitis...
December 5, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27906171/combined-nifuroxazide-and-sat05f-therapy-reduces-graft-versus-host-disease-after-experimental-allogeneic-bone-marrow-transplantation
#3
Huijie Jia, Tiesuo Zhao, Yinghua Ji, Xiaolong Jia, Wenjing Ren, Chen Li, Minming Li, Yali Xiao, Hui Wang, Kailin Xu
Acute graft-versus-host disease (aGvHD) is the major barrier to the broader use of allogenetic hematopoietic stem cells. However, currently these are no highly specific and efficient drugs. Monotherapy is not sufficient and more efficient and safe therapeutic regimen are urgent need. Studies demonstrated TLR9 and Stat3 signal pathways are critical for antigen-presenting cell maturation and T-cell activation, which are important mediators in aGvHD. Specific block these two critical signal pathways using their inhibitors SAT05f and nifuroxazide may be the novel strategies for aGvHD therapy...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27895172/pulmonary-dendritic-cell-subsets-shape-the-respiratory-syncytial-virus-specific-cd8-t-cell-immunodominance-hierarchy-in-neonates
#4
Allison M W Malloy, Tracy J Ruckwardt, Kaitlyn M Morabito, Annie W Lau-Kilby, Barney S Graham
Young infants are generally more susceptible to viral infections and experience more severe disease than do adults. CD8(+) T cells are important for viral clearance, and although often ineffective in neonates they can be protective when adequately stimulated. Using a murine CB6F1/J hybrid model of respiratory syncytial virus (RSV) infection, we previously demonstrated that the CD8(+) T cell immunodominance hierarchy to two RSV-derived epitopes, K(d)M282-90 and D(b)M187-195, was determined by the age at infection...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27888633/toll-like-receptor-9-expression-is-associated-with-breast-cancer-sensitivity-to-the-growth-inhibitory-effects-of-bisphosphonates-in-vitro-and-in-vivo
#5
Jouko Sandholm, Jaakko Lehtimäki, Tamiko Ishizu, Sadanandan E Velu, Jeremy Clark, Pirkko Härkönen, Arja Jukkola-Vuorinen, Aleksi Schrey, Kevin W Harris, Johanna M Tuomela, Katri S Selander
Bisphosphonates are standard treatments for bone metastases. When given in the adjuvant setting, they reduce breast cancer mortality and recurrence in bone but only among post-menopausal patients. Optimal drug use would require biomarker-based patient selection. Such biomarkers are not yet in clinical use. Based on the similarities in inflammatory responses to bisphosphonates and Toll-like receptor (TLR) agonists, we hypothesized that TLR9 expression may affect bisphosphonate responses in cells. We compared bisphosphonate effects in breast cancer cell lines with low or high TLR9 expression...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27865860/human-regulatory-b-cells-control-tfh-response
#6
Achouak Achour, Quentin Simon, Audrey Mohr, Jean-François Séité, Pierre Youinou, Boutahar Bendaoud, Ibtissem Ghedira, Jacques-Olivier Pers, Christophe Jamin
BACKGROUND: Follicular helper T (Tfh) cells support the terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses but their control of Tfh-dependent humoral immune responses is unknown. OBJECTIVE: To assess the role of Breg cells on Tfh development and function. METHODS: Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate Tfh cells. They were co-cultured with B cells to induce their terminal differentiation...
November 16, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27861512/a-rapid-response-humoral-vaccine-platform-exploiting-pre-existing-non-cognate-populations-of-anti-vaccine-or-anti-viral-cd4-t-helper-cells-to-confirm-b-cell-activation
#7
Thomas Hills, Phillip G Jakeman, Robert C Carlisle, Paul Klenerman, Leonard W Seymour, Ryan Cawood
The need for CD4+ T cell responses to arise de novo following vaccination can limit the speed of B cell responses. Populations of pre-existing vaccine-induced or anti-viral CD4+ T cells recognising distinct antigens could be exploited to overcome this limitation. We hypothesise that liposomal vaccine particles encapsulating epitopes that are recognised, after processing and B cell MHCII presentation, by pre-existing CD4+ T cells will exploit this pre-existing T cell help and result in improved antibody responses to distinct target antigens displayed on the particle surface...
2016: PloS One
https://www.readbyqxmd.com/read/27852323/circulating-exosomes-from-patients-with-systemic-lupus-erythematosus-induce-an-proinflammatory-immune-response
#8
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/27849177/the-interplay-of-tlr9-myeloid-cells-and-a20-in-periodontal-inflammation
#9
Katie E Crump, Jennifer C Oakley, Xia Xia-Juan, Theandra C Madu, Swathi Devaki, Erin C Mooney, Sinem E Sahingur
TLR9 deficient (TLR9(-/-)) mice are resistant to periodontitis, a disease characterized by a dysbiotic microbiota and deregulated immune response resulting in tooth loss and various systemic conditions. However, the mechanisms and biological pathways by which TLR9 instigates periodontal inflammation are yet to be identified. In a ligature-induced model of periodontitis, we demonstrate TLR9(-/-) mice exhibited significantly less alveolar bone loss compared to their wild-type (WT) counterparts. Consistent with the disease phenotype, gingival tissues showed significantly more inflammatory cell infiltrate in the WT ligated but not in the TLR9(-/-) ligated mice compared to their unligated controls...
November 14, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27825048/the-effect-of-the-tlr9-ligand-cpg-oligodeoxynucleotide-on-the-protective-immune-response-to-radiation-induced-lung-fibrosis-in-mice
#10
Jing Chen, Xiaoli Tian, Zijie Mei, Yacheng Wang, Ye Yao, Shimin Zhang, Xin Li, Hui Wang, Junhong Zhang, Conghua Xie
CpG-oligodeoxynucleotide (CpG-ODN) is not only reported to protect against airway hyper responsiveness but is also known as a potent vaccine adjuvant for anti-tumor therapy. Little is known about the effect of CpG-ODN in mice with radiation-induced lung fibrosis (RILF), a common late stage form of tissue damage that occurs after thorax radiotherapy (RT). Here, we evaluated the immunomodulatory effects of CpG-ODN on the development of RILF. Mice were divided into four groups: (1) RT, single dose of 12Gy to the whole thorax; (2) CpG, only intraperitoneal injection of CpG-ODN for total 5 weeks; (3) RT+CpG, irradiation plus CpG-ODN treatment before and after irradiation for total 5 weeks; and (4) control (CTL): No RT or CpG-ODN treatment...
November 5, 2016: Molecular Immunology
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
#11
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/27815972/toll-like-receptor-9-expression-and-activation-in-acute-coronary-syndrome-patients-on-dual-anti-platelet-therapy
#12
Kathryn E Hally, Anne C La Flamme, Peter D Larsen, Scott A Harding
INTRODUCTION: The Toll-like receptor 9 (TLR9) pathway can activate platelets but its role in acute coronary syndromes (ACS) is unknown. This study examined TLR9 expression and platelet activation in response to ODN2006, a TLR9 agonist, in healthy subjects and in ACS subjects treated with dual anti-platelet therapy (DAPT). MATERIALS AND METHODS: TLR9 expression was examined in both resting and thrombin receptor activator peptide (TRAP)-activated platelets (1 and 10μM) from healthy and ACS subjects by flow cytometry...
October 29, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27810495/psoriasis-risk-snps-and-their-association-with-hiv-1-control
#13
Joanne Nititham, Rashmi Gupta, Xue Zeng, Wendy Hartogensis, Douglas F Nixon, Steven G Deeks, Frederick M Hecht, Wilson Liao
Human evolution has resulted in selection for genetic polymorphisms beneficial in the defense against pathogens. However, such polymorphisms may have the potential to heighten the risk of autoimmune disease. Here, we investigated whether psoriasis-associated single nucleotide polymorphisms influence host control of HIV-1 infection. We studied psoriasis and viral immune response variants in three HIV-positive cohorts: (1) HIV-1 controllers and non-controllers in the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort (n=366), (2) Individuals with primary HIV infection in the Options cohort (n=675), and (3) HIV-positive injection drug users from the Urban Health Study (UHS) (n=987)...
October 31, 2016: Human Immunology
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
#14
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/27799798/high-dose-irradiation-in-combination-with-toll-like-receptor-9-agonist-cpg-oligodeoxynucleotide-7909-downregulates-pd-l1-expression-via-the-nf-%C3%AE%C2%BAb-signaling-pathway-in-non-small-cell-lung-cancer-cells
#15
Xue Chen, Qi Zhang, Youjun Luo, Caixia Gao, Xibing Zhuang, Guoxiong Xu, Tiankui Qiao
OBJECTIVES: Irradiation resistance appears as local recurrence and distant metastasis in advanced stages of non-small cell lung cancer (NSCLC). High-dose irradiation combined with immunotherapy improved overall survival and local control of NSCLC. This study explored the underlying molecular mechanism by which the effect of high-dose irradiation plus toll-like receptor 9 (TLR9) agonist CpG oligodeoxynucleotide (CpG ODN) 7909 on NSCLC. MATERIALS AND METHODS: NSCLC H460 cells were exposed to constant high-dose irradiation (6...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27799536/intratumoral-injection-of-a-cpg-oligonucleotide-reverts-resistance-to-pd-1-blockade-by-expanding-multifunctional-cd8-t-cells
#16
Shu Wang, Jose Campos, Marilena Gallotta, Mei Gong, Chad Crain, Edwina Naik, Robert L Coffman, Cristiana Guiducci
Despite the impressive rates of clinical response to programmed death 1 (PD-1) blockade in multiple cancers, the majority of patients still fail to respond to this therapy. The CT26 tumor in mice showed similar heterogeneity, with most tumors unaffected by anti-PD-1. As in humans, response of CT26 to anti-PD-1 correlated with increased T- and B-cell infiltration and IFN expression. We show that intratumoral injection of a highly interferogenic TLR9 agonist, SD-101, in anti-PD-1 nonresponders led to a complete, durable rejection of essentially all injected tumors and a majority of uninjected, distant-site tumors...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27798148/rage-enhances-tlr-responses-through-binding-and-internalization-of-rna
#17
Damien Bertheloot, Allison L Naumovski, Pia Langhoff, Gabor L Horvath, Tengchuan Jin, Tsan Sam Xiao, Natalio Garbi, Sudhir Agrawal, Roland Kolbeck, Eicke Latz
Nucleic acid recognition is an important mechanism that enables the innate immune system to detect microbial infection and tissue damage. To minimize the recognition of self-derived nucleic acids, all nucleic acid-sensing signaling receptors are sequestered away from the cell surface and are activated in the cytoplasm or in endosomes. Nucleic acid sensing in endosomes relies on members of the TLR family. The receptor for advanced glycation end-products (RAGE) was recently shown to bind DNA at the cell surface, facilitating DNA internalization and subsequent recognition by TLR9...
October 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27795867/the-role-of-tlr2-tlr4-and-tlr9-in-the-pathogenesis-of-atherosclerosis
#18
REVIEW
Mohsin H K Roshan, Amos Tambo, Nikolai P Pace
Toll-like receptors (TLRs) are key players in the pathogenesis of inflammatory conditions including coronary arterial disease (CAD). They are expressed by a variety of immune cells where they recognize pathogen-associated molecular patterns (PAMPs). TLRs recruit adaptor molecules, including myeloid differentiation primary response protein (MYD88) and TIRF-related adaptor protein (TRAM), to mediate activation of MAPKs and NF-kappa B pathways. They are associated with the development of CAD through various mechanisms...
2016: International Journal of Inflammation
https://www.readbyqxmd.com/read/27795360/local-induction-of-b-cell-il-10-competency-alleviates-inflammation-and-bone-loss-in-ligature-induced-experimental-periodontitis-in-mice
#19
Pei Yu, Yang Hu, Zhiqiang Liu, Toshihisa Kawai, Martin A Taubman, Wei Li, Xiaozhe Han
IL-10-producing B cells (B10 cells) play a critical role in immune system balance by negatively regulating inflammatory responses. This study was to determine the effect of local B10 induction on periodontal inflammation and bone loss in ligature-induced experimental periodontitis in vivo Purified spleen B cells from C57BL/6J mice (8 to 10 weeks old) were cultured with CD40 ligand (CD40L) and Toll-like receptor 9 (TLR9) agonist cytidine-phosphate-guanosine oligodeoxynucleotide (CpG) to determine effective IL-10 induction in vitro Silk ligatures (size 7-0) were tied around the mouse maxillary second molars on Day 0 followed by the injections of CD40L and CpG into the palatal gingiva on Days 3, 6, and 9...
October 17, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27793667/the-role-of-tlr9-in-stress-dependent-autophagy-formation
#20
Jae Sung Lim, Hyeon Sik Kim, Kim Cuc Thi Nguyen, Kyung A Cho
Autophagy is a self-degradation process that is important for balancing energy sources at critical times in development and in response to nutrient stress. Recently, it was report that autophagy is controlled by recognizing conserved pattern recognition receptors (PRRs), including toll-like receptors (TLRs). However, the molecular mechanism of TLRs in autophagy is not well understood. In this study, we found that serum starvation-dependent autophagy was associated with TLR9 activation in the absence of CpG-ODN, which is a specific TLR9 ligand...
October 26, 2016: Biochemical and Biophysical Research Communications
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