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TLR9

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https://www.readbyqxmd.com/read/28742087/type-1-skewed-neuroinflammation-and-vascular-damage-associated-with-orientia-tsutsugamushi-infection-in-mice
#1
Lynn Soong, HeThomas R Shelite, Yan Xing, Harica Kodakandla, Yuejin Liang, Brandon J Trent, Paulina Horton, Kathryn C Smith, Zhenyang Zhao, Jiaren Sun, Donald H Bouyer, Jiyang Cai
BACKGROUND: Scrub typhus is a life-threatening disease, due to infection with O. tsutsugamushi, a Gram-negative bacterium that preferentially replicates in endothelial cells and professional phagocytes. Meningoencephalitis has been reported in scrub typhus patients and experimentally-infected animals; however, the neurological manifestation and its underlying mechanisms remain poorly understood. To address this issue, we focused on Orientia tsutsugamushi Karp strain (OtK), and examined host responses in the brain during lethal versus self-healing scrub typhus disease in our newly established murine models...
July 24, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28729715/inflammatory-monocytes-regulate-th1-oriented-immunity-to-cpg-adjuvanted-protein-vaccines-through-production-of-il-12
#2
S De Koker, L Van Hoecke, A De Beuckelaer, K Roose, K Deswarte, M A Willart, P Bogaert, T Naessens, B G De Geest, X Saelens, B N Lambrecht, J Grooten
Due to their capacity to skew T cell responses towards Th1 oriented immunity, oligonucleotides containing unmethylated CpG motifs (CpG) have emerged as interesting adjuvants for vaccination. Whereas the signalling pathways in response to CpG mediated TLR9 activation have been extensively documented at the level of the individual cell, little is however known on the precise identity of the innate immune cells that govern T cell priming and polarisation to CpG adjuvanted protein antigens in vivo. In this study, we demonstrate that optimal induction of Th1 oriented immunity to CpG adjuvanted protein vaccines requires the coordinated actions of conventional DCs and of monocytes...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724760/uv-radiation-activates-toll-like-receptor-9-expression-in-primary-human-keratinocytes-an-event-inhibited-by-human-papillomavirus-type-38-e6-and-e7-oncoproteins
#3
Laura Pacini, Maria Grazia Ceraolo, Assunta Venuti, Giusi Melita, Uzma A Hasan, Rosita Accardi, Massimo Tommasino
Several lines of evidence indicate that cutaneous human papillomavirus (HPV) types belonging to the beta genus of the HPV phylogenetic tree synergise with UV radiation in the development of skin cancer. Accordingly, the E6 and E7 oncoproteins from some beta HPV types are able to deregulate pathways related to immune response and cellular transformation. Toll-like receptor 9 (TLR9), in addition to playing a role in innate immunity, has been shown to be involved in the cellular stress response. Using primary human keratinocytes (PHKs) as experimental models, we have shown that UV irradiation (and other cellular stresses) activates TLR9 expression...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28716576/tlr9-mediated-conditioning-of-liver-environment-is-essential-for-successful-intrahepatic-immunotherapy-and-effective-memory-recall
#4
Marcin Cebula, Mathias Riehn, Upneet Hillebrand, Ramona F Kratzer, Florian Kreppel, Georgia Koutsoumpli, Toos Daemen, Hansjörg Hauser, Dagmar Wirth
Immune defense against hepatotropic viruses such as hepatitis B (HBV) and hepatitis C (HCV) poses a major challenge for therapeutic approaches. Intrahepatic cytotoxic CD8 T cells that are crucial for an immune response against these viruses often become exhausted resulting in chronic infection. We elucidated the T cell response upon therapeutic vaccination in inducible transgenic mouse models in which variable percentages of antigen-expressing hepatocytes can be adjusted, providing mosaic antigen distribution and reflecting the varying viral antigen loads observed in patients...
July 14, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28715645/characteristics-of-regulatory-b-cells-in-patients-with-chronic-hepatitis-b-virus-infection-in-different-immune-phases
#5
Guiyang Wang, Yong Liu, Rui Huang, Bei Jia, Ran Su, Zhenhua Sun, Chen Tian, Yali Xiong, Juan Xia, Xiaomin Yan, Zhaoping Zhang, Chao Wu
Regulatory B cells (Bregs) are reported to play an important role in the immune responses to chronic hepatitis B virus (HBV) via Toll-like-receptors (TLRs) signaling. We aimed to investigate the characteristics of Bregs and the expressions of TLRs in Bregs in the peripheral blood of different immune phases of patients with chronic HBV infection. In this study, we determined the frequencies of Bregs and TLR9, TLR2, and TLR4 in peripheral blood using flow cytometry and determined the levels of IL-10 in serum with the Human Magnetic Cytokine/Chemokine Bead Panel...
May 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28704709/protective-role-of-surface-toll-like-receptor-9-expressing-neutrophils-in-local-inflammation-during-systemic-inflammatory-response-syndrome-in-mice
#6
Xiuping Meng, Wei Sun, Yunjia Ren, Yue Xiao, Peiyan Zhao, Wenting Lu, Li Hua, Luowei Wang, Liying Wang, Yongli Yu
Clinically, systemic inflammatory response syndrome (SIRS) occurs after serious trauma or sepsis. In sepsis, neutrophils are the major effector cells responsible for eliminating pathogens. However, the role of neutrophils in development of SIRS, especially in local inflammatory area, is controversial. In this study, we established a SIRS mouse model characterized with cytokine-mediated lethal shock by intraperitoneal injection of oligodexynucleotides containing CpG motifs (CpG ODN) in D-galactosamine (D-GalN) sensitized mice based on our previous work and found that abundant neutrophils were rapidly recruited into the peritoneal cavity, where some neutrophils expressed surface TLR9 (sTLR9), defined as sTLR9(+) neutrophils...
July 10, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28704679/ph-sensitive-polymer-modified-liposome-based-immunity-inducing-system-effects-of-inclusion-of-cationic-lipid-and-cpg-dna
#7
Yuta Yoshizaki, Eiji Yuba, Naoki Sakaguchi, Kazunori Koiwai, Atsushi Harada, Kenji Kono
Efficient vaccine carriers for cancer immunotherapy require two functions: antigen delivery to dendritic cells (DCs) and the activation of DCs, a so-called adjuvant effect. We previously reported antigen delivery system using liposomes modified with pH-sensitive polymers, such as 3-methylglutarylated hyperbranched poly(glycidol) (MGlu-HPG), for the induction of antigen-specific immune responses. We reported that inclusion of cationic lipids to MGlu-HPG-modified liposomes activates DCs and enhances antitumor effects...
July 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28703296/correlation-between-tlr2-tlr3-tlr4-and-tlr9-polymorphisms-and-susceptibility-to-and-prognosis-of-severe-hepatitis-among-the-newborns
#8
Xiao Qiu, Yubin Dong, Yaqin Cao, Yingmei Luo
BACKGROUND: This study was aimed to explore how toll-like receptor 2 (TLR2), TLR3, TLR4 and TLR9 influenced the risk and prognosis of severe hepatitis among the Chinese newborns. METHODS: Altogether 135 newborns diagnosed with severe hepatitis and 140 healthy newborns were included in this study. Totally 12 single nucleotide polymorphisms (SNPs) within TLR2, TLR3, TLR4, and TLR9 were chosen and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)...
July 13, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28701256/toll-like-receptor-expression-patterns-in-the-rat-uterus-during-post-partum-involution
#9
Emel Alan, Narin Liman
Toll-like receptors (TLRs) belong to a family of pathogen recognition receptors and play critical roles in detecting and responding to invading pathogens. TLR expression could be significant because, in the uterus, the reproductive tract is an important site of exposure to and infection by pathogens during the post partum involution period. To clarify the expression and localisation patterns of TLRs in the rat uterus on Days 1, 3, 5 and 10 post partum (PP1, PP3, PP5 and PP10 respectively), immunohistochemistry and western blotting were used to analyse TLR1-7, TLR9 and TLR10...
July 13, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28698400/altered-toll-like-receptor-expression-and-function-in-hpv-associated-oropharyngeal-carcinoma
#10
Priscila Lie Tobouti, Robert Bolt, Raghu Radhakrishnan, Suzana Cantanhede Orsini Machado Sousa, Keith D Hunter
Toll-like receptors (TLRs) have been widely investigated due to their importance in the inflammatory response and possible links to tumor promotion/regression and prognosis. In cancers with an infective etiology, such as human papillomavirus (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC), TLR responses may be activated and play a role in tumorigenesis. Our aim was to assess the expression of all TLRs in OPSCC cell lines (both HPV+ and HPV-) by qPCR, Western Blot and flow cytometry and assess their response to TLR ligands lipopolysaccharide (LPS), LPS ultra-pure (LPS-UP) and peptidoglycan (PGN) by analyzing IL-8 and IL-6 production...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28696418/associations-between-functional-polymorphisms-and-response-to-biological-treatment-in-danish-patients-with-psoriasis
#11
N D Loft, L Skov, L Iversen, R Gniadecki, T N Dam, I Brandslund, H J Hoffmann, M R Andersen, R B Dessau, A C Bergmann, N M Andersen, P S Andersen, S Bank, U Vogel, V Andersen
Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28694238/functionalized-bioengineered-spider-silk-spheres-improve-nuclease-resistance-and-activity-of-oligonucleotide-therapeutics-providing-a-strategy-for-cancer-treatment
#12
Anna Karolina Kozlowska, Anna Florczak, Maciej Smialek, Ewelina Dondajewska, Andrzej Mackiewicz, Marcin Kortylewski, Hanna Dams-Kozlowska
Cell-selective delivery and sensitivity to serum nucleases remain major hurdles to the clinical application of RNA-based oligonucleotide therapeutics, such as siRNA. Spider silk shows great potential as a biomaterial due to its biocompatibility and biodegradability. Self-assembling properties of silk proteins allow for processing into several different morphologies such as fibers, scaffolds, films, hydrogels, capsules and spheres. Moreover, bioengineering of spider silk protein sequences can functionalize silk by adding peptide moieties with specific features including binding or cell recognition domains...
July 8, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28687713/tlr9-is-upregulated-in-human-and-murine-nash-pivotal-role-for-inflammatory-recruitment-and-cell-survival
#13
Auvro R Mridha, Fahrettin Haczeyni, Matthew M Yeh, W Geoffrey Haigh, George N Ioannou, Vanessa Barn, Hussam Ajamieh, Leon Adams, Jeffrey M Hamdorf, Narci C Teoh, Geoffrey C Farrell
Background & Aims: TLR9 deletion protects against steatohepatitis due to choline-amino acid depletion and high-fat diet. We measured TLR9 in human NASH livers, and tested whether TLR9 mediates inflammatory recruitment in three murine models of NAFLD. Methods: We assayed TLR mRNA in liver biopsies from bariatric surgery patients. Wildtype (Wt) , appetite-dysregulated Alms1 mutant (foz/foz),Tlr9(-/-), and Tlr9(-/-).foz/foz C57BL6/J mice and bone marrow (BM) chimeras were fed 0.2% cholesterol, high-fat, high sucrose (atherogenic[Ath]) diet or chow, and NAFLD activity score (NAS)/NASH pathology, macrophage/neutrophil infiltration, cytokines/chemokines and cell death markers measured in livers...
July 7, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28686452/immunostimulatory-properties-of-lipid-modified-cpg-oligonucleotides
#14
Chunsong Yu, Myunggi An, Meng Li, Haipeng Liu
Innate immune responses recognizing pathogen associated molecular patterns play important roles in adaptive immunity. As such, ligands which mimic the conserved products of microbial and activate innate immunity are widely used as adjuvants for vaccines. Synthetic single strand oligodeoxynucleotides (ODNs) containing unmethylated cytosine-guanine (CpG) motifs which bind Toll-like receptor 9 (TLR9) are powerful molecular adjuvants, potentiating both humoral and cellular responses. However, CpG ODN's in vitro potency has not been translated to in vivo settings primarily due to issues associated with delivery and toxicity...
July 7, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28680097/attenuation-of-innate-immunity-by-andrographolide-derivatives-through-nf-%C3%AE%C2%BAb-signaling-pathway
#15
Xin Nie, Shao-Ru Chen, Kun Wang, Yuran Peng, Yi-Tao Wang, Decai Wang, Ying Wang, Guo-Chun Zhou
Andrographolide derivatives or analogs exhibit potent anti-inflammatory effects in several disease models through NF-κB activity. In this study, we synthesized different andrographolide derivatives and investigated their effects on the toll-like receptor (TLR)-induced production of pro-inflammatory cytokines. Among these compounds, 3b, 5a, and 5b inhibited both TNF-α/NF-κB and TLR4/NF-κB signaling pathways. Treatment with compounds 3b, 5a, and 5b and their structural analogs, 3a and 6b, suppressed the expression of pro-inflammatory cytokines upon the activation of TLR3 and TLR4 ligands...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28677621/polymorphisms-within-genes-involved-in-regulation-of-the-nf-%C3%AE%C2%BAb-pathway-in-patients-with-rheumatoid-arthritis
#16
Katarzyna Gębura, Jerzy Świerkot, Barbara Wysoczańska, Lucyna Korman, Beata Nowak, Piotr Wiland, Katarzyna Bogunia-Kubik
Genes involved in regulation of the nuclear factor-κB (NF-κB)-pathway are suggested to play a role in pathogenesis of rheumatoid arthritis (RA). In the present study, genetic polymorphisms of TLR2, TLR4, TLR9 and NF-κB1 genes were investigated to assess their associations with RA susceptibility, progression and response to anti-TNF-α therapy. A group of 110 RA patients and 126 healthy individuals were genotyped for TLR2 (rs111200466), TLR4 (rs4986790, rs4986791), TLR9 (rs5743836, rs187084) and NF-κB1 (rs28362491) alleles...
July 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28673462/cell-free-dna-induced-alteration-of-autophagy-response-and-tlr9-signaling-their-relation-to-amelioration-of-dss-colitis
#17
Györgyi Műzes, Anna L Kiss, Zsolt Tulassay, Ferenc Sipos
BACKGROUND: The influence of cell-free DNA (fDNA) administration on the TLR9-autophagy regulatory crosstalk within inflammatory circumstances remains unclear. AIMS: To examine the immunobiologic effects of iv. fDNA injection on the TLR9-mediated autophagy response in murine DSS-colitis. METHODS: Different types of modified fDNAs were administered to DSS-colitic mice. Disease and histological activities, spleen index were measured. Changes of the TLR9-associated and autophagy-related gene expression profiles of lamina proprial cells and splenocytes were assayed by quantitative real-time PCR, and validated by immunohistochemistries...
June 2017: Comparative Immunology, Microbiology and Infectious Diseases
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
#18
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/28652573/extraordinarily-potent-proinflammatory-properties-of-lactoferrin-containing-immunocomplexes-against-human-monocytes-and-macrophages
#19
Lulu Hu, Xiaomin Hu, Kai Long, Chenhui Gao, Hong-Liang Dong, Qiao Zhong, Xiao-Ming Gao, Fang-Yuan Gong
Lactoferrin (LTF), an important first line defense molecule against infection, is a common target for humoral autoimmune reactions in humans. Since LTF is a multifunctional protein capable of activating innate immune cells via various surface receptors, we hypothesized that LTF-containing immune complexes (ICs) (LTF-ICs), likely formed in patients with high titer anti-LTF autoantibodies, could possess unique monocyte/macrophage-activating properties compared with other ICs. ELISA analysis on serum samples from rheumatoid arthritis (RA) patients (n = 80) and healthy controls (n = 35) for anti-LTF autoantibodies confirmed a positive correlation between circulating LTF-specific IgG and RA...
June 26, 2017: Scientific Reports
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
#20
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
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