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https://www.readbyqxmd.com/read/28550425/cpg-oligonucleotide-mediated-co-stimulation-of-mouse-invariant-natural-killer-t-cells-negatively-regulates-their-activation-status
#1
Raveendra R Kulkarni, Alexander Ian Villanueva, Leah R Read, Jennifer T Brisbin, Siddhartha Kumar Bhaumik, Jonathan LaMarre, Kaja Murali-Krishna, Shayan Sharif
Invariant natural killer T (iNKT) cells play important roles in antimicrobial defense and immune-regulation. We have previously shown that iNKT cells express certain toll-like receptors (TLR), and that TLR co-stimulation of iNKT cells in the presence of suboptimal concentrations of T cell receptor (TCR) agonists enhances cellular activation. In the present study, we investigated the regulatory effects of CpG oligonucleotides in mouse primary hepatic and splenic iNKT cells and in DN32.D3 iNKT cells. We show that CpG treatment of iNKT cells in the presence of higher concentrations of TCR agonists (α-GalCer or anti-CD3 mAb) results in the up-regulation of TLR9 in iNKT cells with a concurrent reduction in their cellular activation, as assessed by their production of IL-2, IL-4 and IFN-γ compared with controls...
May 27, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28544067/vitamin-d3-alters-the-expression-of-toll-like-receptors-in-peripheral-blood-mononuclear-cells-of-patients-with-systemic-lupus-erythematosus
#2
Esmaeil Yazdanpanah, Mahmoud Mahmoudi, Maryam Sahebari, Zahra Rezaieyazdi, Seyed-Alireza Esmaeili, Nafiseh Tabasi, Soheila Jaberi, Amirhossein Sahebkar, Maryam Rastin
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by production of inflammatory cytokines and autoreactive antibodies due to the loss of immune tolerance. Recognition of self-nucleic acids by intracellular Toll-like receptors (TLRs) can overactivate immune responses and this abnormal activation of TLRs contributes to the pathogenesis of the disease. In recent years, anti-inflammatory and immunomodulatory effects of 1, 25-dihydroxyvitamin D3 (VitD3) on the immune system has received particular attention...
May 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28542146/the-role-of-extracellular-histone-in-organ-injury
#3
REVIEW
Eleanor Silk, Hailin Zhao, Hao Weng, Daqing Ma
Histones are intra-nuclear cationic proteins that are present in all eukaryotic cells and are highly conserved across species. Within the nucleus, they provide structural stability to chromatin and regulate gene expression. Histone may be released into the extracellular space in three forms: freely, as a DNA-bound nucleosome or as part of neutrophil extracellular traps, and all three can be detected in serum after significant cellular death such as sepsis, trauma, ischaemia/reperfusion injury and autoimmune disease...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28539706/multiple-immunosuppressive-effects-of-cpg-c41-on-intracellular-tlr-mediated-inflammation
#4
Wancheng Liu, Xuejiao Yang, Ning Wang, Shijun Fan, Yuanfeng Zhu, Xinchuan Zheng, Yan Li
A growing body of literature suggests that most chronic autoimmune diseases are associated with inappropriate inflammation mediated by Toll-like receptor (TLR) 3, TLR7/8, or TLR9. Therefore, research into blocking TLR activation to treat these disorders has become a hot topic. Here, we report the immunomodulatory properties of a nonstimulatory CpG-containing oligodeoxynucleotide (CpG-ODN), CpG-c41, which had previously only been known as a TLR9 antagonist. In this study, we found that both in vitro and in vivo CpG-c41 decreased levels of various proinflammatory factors that were induced by single activation or coactivation of intracellular TLRs, but not membrane-bound TLRs, no matter what downstream signal pathways the TLRs depend on...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28539427/tlr-induced-murine-dendritic-cell-dc-activation-requires-dc-intrinsic-complement
#5
Joong-Hyuk Sheen, Michael G Strainic, Jinbo Liu, Weijia Zhang, Zhengzi Yi, M Edward Medof, Peter S Heeger
Induction of proinflammatory T cell immunity is augmented by innate dendritic cell (DC) maturation commonly initiated by TLR signaling. We demonstrate that ligation of TLR3, TLR4, and TLR9 induces murine DC production of complement components and local production of the anaphylatoxin C5a. In vitro, ex vivo, and in vivo analyses show that TLR-induced DC maturation, as assessed by surface phenotype, expression profiling by gene array, and functional ability to stimulate T cell responses, requires autocrine C3a receptor and C5a receptor (C3ar1/C5ar1) signaling...
May 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28536249/bronchial-inflammation-and-bacterial-load-in-stable-copd-is-associated-with-tlr4-overexpression
#6
Antonino Di Stefano, Fabio L M Ricciardolo, Gaetano Caramori, Ian M Adcock, Kian Fan Chung, Peter J Barnes, Paola Brun, Andrea Leonardi, Filippo Andò, Davide Vallese, Isabella Gnemmi, Luisella Righi, Francesco Cappello, Bruno Balbi
Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial mucosa of subjects with stable COPD of different severity (n=34), control smokers (n=12) and nonsmokers (n=12)...
May 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28533357/tlr9-expression-and-secretion-of-lif-by-prostate-cancer-cells-stimulates-accumulation-and-activity-of-polymorphonuclear-mdscs
#7
Haejung Won, Dayson Moreira, Chan Gao, Priyanka Duttagupta, Xingli Zhao, Edwin Manuel, Don Diamond, Yate-Ching Yuan, Zheng Liu, Jeremy Jones, Massimo D'Apuzzo, Sumanta Pal, Marcin Kortylewski
Proinflammatory signals promote prostate tumorigenesis and progression, but their origins and downstream effects remain unclear. We recently demonstrated that the expression of an innate immune receptor, TLR9, by prostate cancer cells is critical for their tumor-propagating potential. We investigated whether cancer cell-intrinsic TLR9 signaling alters composition of the prostate tumor microenvironment. We generated Ras/Myc (RM9) and Myc-driven (Myc-CaP) prostate cancer cells expressing the tetracycline-inducible gene Tlr9 (Tlr9(ON) ) or the control LacZ (LacZ(ON) )...
May 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28530246/short-single-stranded-dna-degradation-products-augment-the-activation-of-toll-like-receptor-9
#8
Jelka Pohar, Duško Lainšček, Karolina Ivičak-Kocjan, Miša-Mojca Cajnko, Roman Jerala, Mojca Benčina
Toll-like receptors encounter a diversity of degradation products in endosomes. TLR7 and TLR8 have been shown to be activated by RNA degradation products. Here we show that although TLR9 requires single-stranded DNA longer than 20 nucleotides for a robust response, TLR9 activation is augmented by CpG-containing oligodeoxyribonucleotides (sODNs) as short as 2 nucleotides, which, by themselves, do not induce activation in cell cultures, as well as in mice. sODNs also activate human TLR9 in combination with ODNs containing a single CpG motif that by themselves do not activate human TLR9...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28528372/associations-between-ptpn22-and-tlr9-polymorphisms-and-systemic-lupus-erythematosus-a-comprehensive-meta-analysis
#9
Li-Ya Hu, Zhi Cheng, Bo Zhang, Qiong Yin, Xiao-Wei Zhu, Pian-Pian Zhao, Ming-Yu Han, Xiao-Bo Wang, Hou-Feng Zheng
Previous studies have explored the relationship of PTPN22 and TLR9 polymorphisms with systemic lupus erythematosus (SLE). In consideration of the population stratification, conflicting results and updating data, we conducted a comprehensive meta-analysis, which consists of a total of 17 research articles (9120 cases and 11,724 controls) for PTPN22 and 20 articles (including up to 2808 cases and 3386 controls) for TLR9. Significant association was verified between PTPN22 rs2476601 and SLE in the overall population (OR = 1...
May 20, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28518215/the-tlr9-signaling-pathway-regulates-mr1-mediated-bacterial-antigen-presentation-in-b-cells
#10
Jianyun Liu, Randy R Brutkiewicz
Mucosal-associated invariant T (MAIT) cells are conserved T cells that express a semi-invariant TCR (Vα7.2 in humans and Vα19 in mice). The development of MAIT cells requires the antigen (Ag) presenting MHC-related protein 1 (MR1), as well as commensal bacteria. The mechanisms that regulate the functional expression of MR1 molecules and their loading with bacterial Ag in APCs are largely unknown. We have found that treating B cells with the TLR9 agonist CpG increases MR1 surface expression. Interestingly, activation of TLR9 by CpG-A (but not CpG-B) enhances MR1 surface expression...
May 18, 2017: Immunology
https://www.readbyqxmd.com/read/28516729/proteome-analysis-of-duck-tembusu-virus-dtmuv-infected-bhk-21-cells
#11
Xin Sun, Shengyu Wang, Xian Lin, Lianzhong Zhao, Dan Zhang, Chenyang Yi, Xiaomei Sun, Huanchun Chen, Meilin Jin
Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused huge economic losses to the duck industry in China since 2010. Moreover, the infection has spread rapidly, posing a potential public health concern. In this study, iTRAQ approach was firstly used to quantitatively identify differentially expressed cellular proteins in DTMUV-infected BHK-21 cells which are usually employed to produce veterinary vaccines for DTMUV, as well as other flaviviruses by serial passage. We identified 192 differentially expressed cellular proteins, including 11 upregulated and 8 downregulated proteins at 24 h postinfection (hpi), as well as 25 upregulated and 151 downregulated proteins at 48 hpi, of which TLR9, DDX3X, and DDX5 may play important roles in virus propagation...
May 17, 2017: Proteomics
https://www.readbyqxmd.com/read/28508449/satellite-glial-cells-in-human-trigeminal-ganglia-have-a-broad-expression-of-functional-toll-like-receptors
#12
Johanna G Mitterreiter, Werner J D Ouwendijk, Monique van Velzen, Gijsbert P van Nierop, Albert D M E Osterhaus, Georges M G M Verjans
Toll-like receptors (TLRs) orchestrate immune responses to a wide variety of danger- and pathogen-associated molecular patterns. Compared to the central nervous system (CNS), expression profile and function of TLRs in the human peripheral nervous system (PNS) are ill-defined. We analyzed TLR expression of satellite glial cells (SGCs) and microglia, glial cells predominantly involved in local immune responses in ganglia of the human PNS and normal-appearing white matter (NAWM) of the CNS, respectively. Ex vivo flow cytometry analysis of cell suspensions obtained from human cadaveric trigeminal ganglia (TG) and NAWM showed that both SGCs and microglia expressed TLR1-5, TLR7 and TLR9, although expression levels varied between these cell types...
May 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28507081/reversion-of-anergy-signatures-in-clonal-cd21low-b-cells-of-mixed-cryoglobulinemia-after-clearance-of-hcv-viremia
#13
Martina Del Padre, Laura Todi, Milica Mitrevski, Ramona Marrapodi, Stefania Colantuono, Massimo Fiorilli, Milvia Casato, Marcella Visentini
Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of IgM(+)CD27(+) B cells. These cells display both the features of anergy induced by continual engagement of the B cell receptor (BCR), such as high expression of phosphorylated extracellular signal regulated kinase (pERK) and reduced lifespan, and of virus-specific exhaustion such as CD21(low) phenotype and defective response to ligation of BCR and Toll-like receptor 9 (TLR9). Usually MC regresses after eradication of HCV with interferon, whose immunomodulatory activity might contribute to this effect...
May 15, 2017: Blood
https://www.readbyqxmd.com/read/28505514/tlr4-supports-the-expansion-of-fasl-cd5-cd1d-hi-regulatory-b-cells-which-decreases-in-contact-hypersensitivity
#14
Keng Wang, Lei Tao, Jianbing Su, Yueyang Zhang, Binhua Zou, Yiyuan Wang, Min Zou, Nana Chen, Linsheng Lei, Xiaojuan Li
Certain B cells termed as "regulatory B cells" (Bregs) can suppress the ongoing immune responses and a splenic CD5(+)CD1d(hi) Breg subset identified earlier was shown to exert its regulatory functions through secretion of IL-10. Though FasL expression is an alternative mechanism of immune suppression used by B cells, little is known about the FasL expressing CD5(+)CD1d(hi) Bregs. In this study, we isolated splenocytes or splenic CD19(+) B cells and compared the efficiency of toll-like receptor(TLR)4 ligand (lipopolysaccharide) with TLR9 ligand (CpG), anti-CD40 and TLR9 ligand (CpG) plus anti-CD40 on the FasL expression of splenic CD5(+)CD1d(hi) Bregs by flow cytometry...
May 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28500897/genetic-alterations-within-tlr-genes-in-development-of-toxoplasma-gondii-infection-among-polish-pregnant-women
#15
Wioletta Wujcicka, Jan Wilczyński, Dorota Nowakowska
PURPOSE: The research was conducted to evaluate the role of genotypes, haplotypes and multiple-SNP variants in the range of TLR2, TLR4 and TLR9 single nucleotide polymorphisms (SNPs) in the development of Toxoplasma gondii infection among Polish pregnant women. MATERIAL AND METHODS: The study was performed for 116 Polish pregnant women, including 51 patients infected with T. gondii, and 65 age-matched control pregnant individuals. Genotypes in TLR2 2258 G>A, TLR4 896 A>G, TLR4 1196 C>T and TLR9 2848 G>A SNPs were estimated by self-designed, nested PCR-RFLP assays...
May 10, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28500073/fc%C3%AE-riiia-signaling-modulates-endosomal-tlr-responses-in-human-cd4-t-cells
#16
Anil K Chauhan
Recognition of Ab-opsonized pathogens by immune cells triggers both TLR and Fc receptor signaling. Fc receptors endocytose modified nucleic acids bound to Abs and deliver them to endosomes, where they are recognized by nucleic acid-sensing TLRs (NA-TLRs). We show that in CD4(+) T cells, NA-TLRs, TLR3, TLR8, and TLR9 are upregulated by FcγRIIIa-pSyk cosignaling and localize with FcγRIIIa on the cell surface. TLR9 accumulates on the cell surface, where it recognizes CpG oligonucleotide 2006. Subcellular location of NA-TLRs is a key determinant in discriminating self versus viral nucleic acid...
May 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28500069/b-cell-activity-is-impaired-in-human-and-mouse-obesity-and-is-responsive-to-an-essential-fatty-acid-upon-murine-influenza-infection
#17
Rasagna Kosaraju, William Guesdon, Miranda J Crouch, Heather L Teague, E Madison Sullivan, Erik A Karlsson, Stacey Schultz-Cherry, Kymberly Gowdy, Lance C Bridges, Lauren R Reese, P Darrell Neufer, Michael Armstrong, Nichole Reisdorph, J Justin Milner, Melinda Beck, Saame Raza Shaikh
Obesity is associated with increased risk for infections and poor responses to vaccinations, which may be due to compromised B cell function. However, there is limited information about the influence of obesity on B cell function and underlying factors that modulate B cell responses. Therefore, we studied B cell cytokine secretion and/or Ab production across obesity models. In obese humans, B cell IL-6 secretion was lowered and IgM levels were elevated upon ex vivo anti-BCR/TLR9 stimulation. In murine obesity induced by a high fat diet, ex vivo IgM and IgG were elevated with unstimulated B cells...
May 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28497211/association-of-toll-like-receptor-gene-polymorphisms-and-its-interaction-with-hpv-infection-in-determining-the-susceptibility-of-cervical-cancer-in-chinese-han-population
#18
Ye Jin, Shuang Qiu, Na Shao, Jianhua Zheng
The aim of the study is to investigate the association of several single-nucleotide polymorphisms (SNPs) within Toll-like receptors (TLRs) gene and additional gene-gene and gene-human papillomavirus (HPV) infection interaction with cervical cancer risk. A total of 1262 participants are selected, including 420 cervical cancer patients and 842 control participants. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among five SNPs within TLR gene and HPV infection...
May 11, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28495789/dietary-nondigestible-oligosaccharides-and-bifidobacterium-breve-m-16v-suppress-allergic-inflammation-in-intestine-via-targeting-dendritic-cell-maturation
#19
Sander de Kivit, Atanaska I Kostadinova, JoAnn Kerperien, Mary E Morgan, Veronica Ayechu Muruzabal, Gerard A Hofman, Leon M J Knippels, Aletta D Kraneveld, Johan Garssen, Linette E M Willemsen
Dietary intervention with short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS) and Bifidobacterium breve M-16V (Bb) (GF/Bb) suppresses food allergic symptoms in mice, potentially via intestinal epithelial cell (IEC)-derived galectin-9. Furthermore, in vitro studies showed galacto- and fructo-oligosaccharides (GF) to enhance the immunomodulatory capacity of a TLR9 ligand representing bacterial CpG DNA when exposed to IEC. In this study, we investigated whether GF/Bb modulates dendritic cells (DCs) and subsequent Th2 and regulatory T cell (Treg) frequency in the small intestinal lamina propria (SI-LP)...
May 11, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28490840/toll-like-receptor-9-promotes-survival-in-serca2a-ko-heart-failure-mice
#20
Yangchen Dhondup, Ivar Sjaastad, Øystein Sandanger, Jan Magnus Aronsen, Muhammad Shakil Ahmed, Håvard Attramadal, Alexandra Vanessa Finsen, Lili Zhang, Trine Ranheim, Katrine Alfsnes, Pål Aukrust, Geir Christensen, Arne Yndestad, Leif Erik Vinge
Aim. Inflammation is important in heart failure (HF). The role of the immune receptor toll-like receptor 9 (TLR9) in HF is not understood and not investigated in diastolic HF. We investigated the role of TLR9 in a murine diastolic HF model caused by cardiomyocyte SERCA2a excision. Methods and Results. We crossed SERCA2a KO and TLR9 KO mice to generate four mouse lines. Tamoxifen-induced cardiomyocyte SERCA2a gene excision was carried out in mice, causing diastolic HF. After 7.6 weeks, cardiac functions and dimensions were analyzed by echocardiography and heart tissues were processed...
2017: Mediators of Inflammation
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