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TLR9

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https://www.readbyqxmd.com/read/28334710/prevention-of-tlr9-pathway-in-warm-ischemia-in-porcine-donor-liver-after-cardiac-death
#1
Zigong Shao, Baoping Jiao, Dehui Yi, Tingting Liu, Qi Pan, Ying Cheng, Hao Liu
OBJECTIVE: To investigate effect of warm ischemia after cardiac death on activation of TLR9 pathway in porcine liver. METHODS: Donor of cardiac death (DCD) model was established with Duroc, Landrace, Large White crossbred pigs. Liver tissues from the animals were harvested at 0, 5, 10, 15, 25 and 30 minutes after warm ischemia for analysis of expression of TLR9, IRF7, IFN-β, and TNF-α at mRNA and protein levels by real-time PCR and western blot, respectively, and for assessment of NF-κB/DNA binding activity by western blot detection of p65 protein...
March 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28329286/short-course-tlr9-agonist-treatment-impacts-innate-immunity-and-plasma-viremia-in-individuals-with-hiv-infection
#2
Line Vibholm, Mariane H Schleimann, Jesper F Højen, Thomas Benfield, Rasmus Offersen, Katrine Rasmussen, Rikke Olesen, Anders Dige, Jørgen Agnholt, Judith Grau, Maria Buzon, Burghardt Wittig, Mathias Lichterfeld, Andreas Munk Petersen, Xutao Deng, Mohammed Abdel-Mohsen, Satish K Pillai, Sofie Rutsaert, Wim Trypsteen, Ward De Spiegelaere, Linos Vandekerchove, Lars Østergaard, Thomas A Rasmussen, Paul W Denton, Martin Tolstrup, Ole S Søgaard
Background: Treatment with latency reversing agents (LRA) enhances HIV-1 transcription in vivo but only leads to modest reductions in the size of the reservoir, possibly due to insufficient immune-mediated elimination of infected cells. We hypothesized that a single drug molecule - a novel toll-like receptor 9 (TLR9) agonist, MGN1703 - could function as an enhancer of innate immunity and an LRA in vivo. Methods: We conducted a single-arm, open-label study, where 15 virologically suppressed HIV-1 infected individuals on antiretroviral therapy received 60 mg MGN1703 s...
March 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28323128/fecal-microbiota-transplantation-fmt-could-reverse-the-severity-of-experimental-necrotizing-enterocolitis-nec-via-oxidative-stress-modulation
#3
Xiaomei Li, Xiaowen Li, Qingjuan Shang, Zongwei Gao, Fabao Hao, Hongjie Guo, Chunbao Guo
Fecal microbiota transplantation (FMT) has been used successfully to treat a variety of gastroenterological diseases. The alterations of microbiota in mouse models of necrotizing enterocolitis (NEC) as well as in patients suggested the possibility of treating NEC with FMT. Here we show that FMT caused an improvement in the histopathology and symptoms of NEC in WT mice, but not Grx1-/- mice. FMT eliminated O2(•)- production and promoted NO production in experimental NEC mice though the modulation of S-glutathionylation of eNOS (eNOS-SSG)...
March 16, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28321710/association-between-tlr9-rs5743836-polymorphism-and-risk-of-recurrent-venous-thromboembolism
#4
Abrar Ahmad, Kristina Sundquist, Bengt Zöller, Peter J Svensson, Jan Sundquist, Ashfaque A Memon
Recent gene knockout studies on mice have shown the role of toll-like receptor 9 (TLR9) in resolution of venous thromboembolism (VTE) through sterile inflammation. However, the role of a putative functional TLR9 polymorphism (rs5743836) in risk assessment of VTE recurrence remains unknown. The aim of our study was to investigate the TLR9 rs5743836 polymorphism in VTE patients and its association with the risk of VTE recurrence. We analyzed TLR9 rs5743836 polymorphism in Malmö thrombophilia study patients; a prospective follow-up study of 1465 VTE patients by Taqman PCR...
March 20, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28319098/irap-endosomes-restrict-tlr9-activation-and-signaling
#5
Joel Babdor, Delphyne Descamps, Aimé Cézaire Adiko, Mira Tohmé, Sophia Maschalidi, Irini Evnouchidou, Luiz Ricardo Vasconcellos, Mariacristina De Luca, Francois-Xavier Mauvais, Meriem Garfa-Traore, Melanie M Brinkmann, Michel Chignard, Bénédicte Manoury, Loredana Saveanu
The retention of intracellular Toll-like receptors (TLRs) in the endoplasmic reticulum prevents their activation under basal conditions. TLR9 is activated by sensing ligands in specific endosomal-lysosomal compartments. Here we identified IRAP(+) endosomes as major cellular compartments for the early steps of TLR9 activation in dendritic cells (DCs). Both TLR9 and its ligand, the dinucleotide CpG, were present as cargo in IRAP(+) endosomes. In the absence of the aminopeptidase IRAP, the trafficking of CpG and TLR9 to lysosomes and signaling via TLR9 were enhanced in DCs and in mice following bacterial infection...
March 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28316602/toll-like-receptor-ligand-based-vaccine-adjuvants-require-intact-myd88-signaling-in-antigen-presenting-cells-for-germinal-center-formation-and-antibody-production
#6
Munir M Mosaheb, Michael L Reiser, Lee M Wetzler
Vaccines are critical in the fight against infectious diseases, and immune-stimulating adjuvants are essential for enhancing vaccine efficacy. However, the precise mechanisms of action of most adjuvants are unknown. There is an urgent need for customized and adjuvant formulated vaccines against immune evading pathogens that remain a risk today. Understanding the specific role of various cell types in adjuvant-induced protective immune responses is vital for an effective vaccine design. We have investigated the role of cell-specific MyD88 signaling in vaccine adjuvant activity in vivo, using Neisserial porin B (PorB), a TLR2 ligand-based adjuvant, compared with an endosomal TLR9 ligand (CpG) and toll-like receptor (TLR)-independent (alum, MF59) adjuvants...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28303762/tlr9-based-immunotherapy-for-the-treatment-of-allergic-diseases
#7
Shokrollah Farrokhi, Narjes Abbasirad, Ali Movahed, Hossein Ali Khazaei, Masoud Pishjoo, Nima Rezaei
Toll-like receptors (TLRs), a family of pattern recognition receptors expressed on many cell types of innate immunity, recognize the pathogen-associated molecular patterns of microbes. The hygiene hypothesis suggests that a reduced microbial exposure in early childhood increases the susceptibility to allergic diseases due to deviation in development of the immune system. TLRs are key roles in the right and healthy direction of adaptive immunity with the induction of T-helper 2 toward Th1 immune responses and regulatory T cells...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28299776/toll-like-receptors-elicit-different-recruitment-kinetics-of-monocytes-and-neutrophils-in-mouse-acute-inflammation
#8
Beat A Imhof, Stephane Jemelin, Yalin Emre
Leukocyte recruitment is an important process in combatting pathogens. The largest class of circulating leukocytes are neutrophils, which rapidly invade inflamed tissue, followed by inflammatory Ly6C(+) monocytes. Ly6C(low) monocytes patrol the endothelial wall routinely in the steady state. We recently reported early luminal recruitment of Ly6C(low) monocytes, which preceded and orchestrated neutrophil arrival and extravasation in response to TLR7/8-mediated vascular inflammation. Here we dissected the kinetics of recruitment of monocytes and neutrophils and examined the dynamics of Ly6C(low) monocytes in response to several other Toll-like receptor (TLR) agonists, using intravital confocal microscopy...
March 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28299026/the-immunomodulatory-effect-of-bone-marrow-mesenchymal-stem-cells-on-expression-of-tlr3-and-tlr9-in-mice-dendritic-cells
#9
L Sadeghi, M H Karimi, E Kamali-Sarvestani, N Azarpira, M Shariati
BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells with immunomodulatory effect on immune cells including dendritic cells (DCs). DCs are the most potent antigen-presenting cells (APC). MSCs have been found to modulate both differentiation and function of DCs. DCs express a broad range of Toll-like receptors (TLR), which play a critical role in DCs maturation and function. OBJECTIVE: To evaluate expression level of TLR3 and TLR9 transcripts in DCs following treatment with MSCs supernatant...
2017: International Journal of Organ Transplantation Medicine
https://www.readbyqxmd.com/read/28295449/hepatic-mtdna-tlr9-microrna-223-forms-a-negative-feedback-loop-to-limit-neutrophil-over-activation-and-acetaminophen-hepatotoxicity
#10
Yong He, Dechun Feng, Man Li, Yanhang Gao, Teresa Ramirez, Haixia Cao, Seung-Jin Kim, Yang Yang, Yan Cai, Cynthia Ju, Hua Wang, Jun Li, Bin Gao
Acetaminophen (APAP) overdose is a leading cause of acute liver failure worldwide, in which mitochondrial DNA (mtDNA) released by damaged hepatocytes activates neutrophils via the binding of TLR9, further aggravating liver injury. Here, we demonstrated that mtDNA/TLR9 also activates a negative feedback pathway via the induction of microRNA-223 (miR-223) to limit neutrophil over-activation and liver injury. After injection of APAP in mice, levels of miR-223, the most abundant miRNAs in neutrophils, were highly elevated in neutrophils...
March 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28295207/human-gestation-associated-tissues-express-functional-cytosolic-nucleic-acid-sensing-pattern-recognition-receptors
#11
Aled H Bryant, Georgina E Menzies, Louis M Scott, Samantha Spencer-Harty, Lleucu B Davies, Rachel A Smith, Ruth H Jones, Catherine A Thornton
The role of viral infections in adverse pregnancy outcomes has gained interest in recent years. Innate immune pattern recognition receptors (PRRs) and their signalling pathways that yield a cytokine output in response to pathogenic stimuli have been postulated to link infection at the maternal-fetal interface and adverse pregnancy outcomes. The objective of this study was to investigate the expression and functional response of nucleic acid ligand responsive Toll-like receptors (TLR3, 7, 8 and 9), and retinoic acid-inducible gene 1 (RIG-I)-like receptors (RIG-I, MDA5 and LGP2) in human term gestation-associated tissues (placenta, choriodecidua and amnion) using an explant model...
March 13, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28289714/bile-acids-initiate-cholestatic-liver-injury-by-triggering-a-hepatocyte-specific-inflammatory-response
#12
Shi-Ying Cai, Xinshou Ouyang, Yonglin Chen, Carol J Soroka, Juxian Wang, Albert Mennone, Yucheng Wang, Wajahat Z Mehal, Dhanpat Jain, James L Boyer
Mechanisms of bile acid-induced (BA-induced) liver injury in cholestasis are controversial, limiting development of new therapies. We examined how BAs initiate liver injury using isolated liver cells from humans and mice and in-vivo mouse models. At pathophysiologic concentrations, BAs induced proinflammatory cytokine expression in mouse and human hepatocytes, but not in nonparenchymal cells or cholangiocytes. These hepatocyte-specific cytokines stimulated neutrophil chemotaxis. Inflammatory injury was mitigated in Ccl2(-/-) mice treated with BA or after bile duct ligation, where less hepatic infiltration of neutrophils was detected...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28288138/muc1-c-integrates-pd-l1-induction-with-repression-of-immune-effectors-in-non-small-cell-lung-cancer
#13
A Bouillez, H Rajabi, C Jin, M Samur, A Tagde, M Alam, M Hiraki, T Maeda, X Hu, D Adeegbe, S Kharbanda, K-K Wong, D Kufe
Immunotherapeutic approaches, particularly programmed death 1/programmed death ligand 1 (PD-1/PD-L1) blockade, have improved the treatment of non-small-cell lung cancer (NSCLC), supporting the premise that evasion of immune destruction is of importance for NSCLC progression. However, the signals responsible for upregulation of PD-L1 in NSCLC cells and whether they are integrated with the regulation of other immune-related genes are not known. Mucin 1 (MUC1) is aberrantly overexpressed in NSCLC, activates the nuclear factor-κB (NF-κB) p65ZEB1 pathway and confers a poor prognosis...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28285125/gene-expression-values-of-pattern-recognition-receptors-in-porcine-leukocytes-and-their-response-to-salmonella-enterica-serovar-typhimurium-infection
#14
Alena Osvaldova, Hana Stepanova, Martin Faldyna, Jan Matiasovic
Pattern-recognition receptors (PRRs) recognize pathogen-associated molecular patterns and play an important role in triggering innate immune responses. PRRs distribution and function is well documented in mice and humans, but studies in pigs are scarce. Salmonella enterica serovar Typhimurium is common pathogen found in pigs and was used as a model for interaction with PRRs. This study investigated expression of PRRs in porcine leukocyte subpopulations at the mRNA level. Eight subpopulations of leukocytes comprising NK cells, Th, Tc, double positive T cells and γδ T cells, B cells, monocytes and neutrophils were sorted, and the expression of 12 PRRs was measured, including selected Toll-like receptors and their co-receptors, NOD-like receptor NOD2, RP-105, CD14, and dectin...
March 1, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28283566/human-plasmacytoid-dendritic-cells-display-and-shed-b-cell-maturation-antigen-upon-tlr-engagement
#15
Elisabeth Schuh, Andrea Musumeci, Franziska S Thaler, Sarah Laurent, Joachim W Ellwart, Reinhard Hohlfeld, Anne Krug, Edgar Meinl
The BAFF-APRIL system is best known for its control of B cell homeostasis, and it is a target of therapeutic intervention in autoimmune diseases and lymphoma. By analyzing the expression of the three receptors of this system, B cell maturation Ag (BCMA), transmembrane activator and CAML interactor, and BAFF receptor, in sorted human immune cell subsets, we found that BCMA was transcribed in plasmacytoid dendritic cells (pDCs) in both blood and lymphoid tissue. Circulating human pDCs contained BCMA protein without displaying it on the cell surface...
March 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28281905/implications-of-toll-like-receptors-in-ebola-infection
#16
Amene Saghazadeh, Nima Rezaei
The potential roles of toll-like receptors (TLRs) in immunopathogenesis of Ebola virus disease should be unraveled to provoke possible prophylactic or therapeutic implications of TLRs for EVD. Areas covered: The Ebola virus (EBOV) infection virtually paralyses all the main mechanisms responsible for induction of type I interferon (IFN-I) response. To summarize, EBOV infection interferes with: a) the TIR-domain-containing adapter-inducing interferon-β (TRIF) pathway that is mediated by TLR3 and TLR4 signaling; b) the interferon regulatory factor 7 (IRF7) pathway that is stimulated by TLR7 and TLR9; c) the intracellular signaling that is induced by retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLRs); and d) the autocrine/paracrine feedback loop that is mediated by the IFN-stimulated gene factor 3 (ISGF3) complex...
April 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28279806/fish-skeletal-muscle-tissue-is-an-important-focus-of-immune-reactions-during-pathogen-infection
#17
Cristián A Valenzuela, Rodrigo Zuloaga, Matías Poblete-Morales, Tamara Vera-Tobar, Luis Mercado, Ruben Avendaño-Herrera, Juan Antonio Valdés, Alfredo Molina
Skeletal muscle in mammals can express and secrete immune-related molecules during pathogen infection. Despite in fish is known that classical immune tissues participate in innate immunity, the role of skeletal muscle in this function is poorly understood. To determine the immunocompetence of fish skeletal muscle, juvenile fine flounder (Paralichthys adpersus) were challenged with Vibrio ordalii. Different Toll-like receptors, pro-inflammatory cytokines (TNFα, Il-1β, and IL-8), and immune-effector molecules (NKEF and the antimicrobial peptides hepcidin and LEAP-2) were analyzed...
March 7, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28278279/toll-like-receptor-9-suppresses-lupus-disease-in-fas-sufficient-mrl-mice
#18
Kevin M Nickerson, Yujuan Wang, Sheldon Bastacky, Mark J Shlomchik
Genetic deficiency in TLR9 accelerates pathogenesis in the spontaneous polygenic MRL.Faslpr murine model of systemic lupus erythematosus, despite the absence of anti-nucleosome autoantibodies. However, it could be argued that this result was dependent on Fas-deficiency rather than lupus-promoting genes in the MRL genetic background. Here we report the effects of TLR9 deficiency on autoimmune disease independent of the lpr mutation in Fas by characterizing Tlr9-/- and Tlr9+/+ mice on the Fas-intact MRL/+ genetic background...
2017: PloS One
https://www.readbyqxmd.com/read/28275186/cpg-in-combination-with-an-inhibitor-of-notch-signaling-suppresses-fi-rsv-enhanced-airway-hyperresponsiveness-and-inflammation-through-inhibiting-th17-memory-responses-and-promoting-tissue-resident-memory-cells-in-lungs
#19
Lei Zhang, Hongyong Li, Yan Hai, Wei Yin, Wenjian Li, Boyang Zheng, Xiaomin Du, Na Li, Zhengzheng Zhang, Yuqing Deng, Ruihong Zeng, Lin Wei
Respiratory syncytial virus (RSV) is the leading cause of childhood hospitalizations. The formalin-inactivated RSV (FI-RSV) vaccine enhanced respiratory disease (ERD) has been an obstacle to the development of a safe and effective killed RSV vaccine. Agonists of Toll-like receptor (TLR) have been shown to regulate immune responses induced by FI-RSV. Notch signaling plays critical roles during the differentiation and effector function phases of innate and adaptive immune responses. Cross-talk between TLR and Notch signaling pathways results in fine tuning of TLR-triggered innate inflammatory responses...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28272460/nucleic-acid-based-polymers-effective-against-hepatitis-b-virus-infection-in-patients-don-t-harbor-immunostimulatory-properties-in-primary-isolated-liver-cells
#20
Catherine Isabell Real, Melanie Werner, Andreas Paul, Guido Gerken, Joerg Friedrich Schlaak, Andrew Vaillant, Ruth Broering
Nucleic acid polymers (NAPs) block the release of subviral particles from hepatocytes, a mechanism consistent with their antiviral activity against hepatitis B virus (HBV) in patients. Analysis of immunostimulatory properties of NAPs were conducted with several NAP species: REP 2006, the prototypic degenerate NAP [dN]40, containing TLR9-stimulatory CpG; REP 2055 a clinically active NAP with a sequence [dAdC]20 devoid of CpG content; REP 2139 (also clinically active) and REP 2165 (REP 2055 analogues further rendered immunologically inactive by replacing cytidine with 5-methylcytidine and incorporating 2'-O methylation of riboses)...
March 8, 2017: Scientific Reports
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