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https://www.readbyqxmd.com/read/28748131/an-in-vitro-investigation-of-immunomodulatory-properties-of-lactobacillus-plantarum-and-l-delbrueckii-cells-and-their-extracellular-polysaccharides
#1
Mana Kishimoto, Ryohei Nomoto, Masashi Mizuno, Ro Osawa
Many probiotic lactobacilli and their extracellular polysaccharides (EPS) have beneficial immunological properties. However, it is unclear how they elicit the host immune response. We thus investigated the immunological properties of UV-killed Lactobacillus delbrueckii TU-1 and L. plantarum KM-9 cells as well as their extracellular polysaccharides (EPSs). High-performance liquid chromatography and ion exchange chromatography analyses showed that their EPSs differ in sugar composition and sugar fractionation...
2017: Bioscience of Microbiota, Food and Health
https://www.readbyqxmd.com/read/28747347/trim8-negatively-regulates-tlr3-4-mediated-innate-immune-response-by-blocking-trif-tbk1-interaction
#2
Wen Ye, Ming-Ming Hu, Cao-Qi Lei, Qian Zhou, Heng Lin, Ming-Shun Sun, Hong-Bing Shu
TLR-mediated signaling pathways play critical roles in host defense against microbials. However, dysregulation of innate immune and inflammatory responses triggered by TLRs would result in harmful damage to the host. Using a Trim8 gene-knockout mouse model, we show that tripartite motif (TRIM) 8 negatively regulates TLR3- and TLR4-mediated innate immune and inflammatory responses. TRIM8 deficiency leads to increased polyinosinic-polycytidylic acid- and LPS-triggered induction of downstream anti-microbial genes including TNF, Il6, Rantes, and Ifnb, evaluated serum cytokine levels, and increased susceptibility of mice to polyinosinic-polycytidylic acid- and LPS-induced inflammatory death as well as Salmonella typhimurium infection-induced loss of body weight and septic shock...
July 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28747344/the-small-rho-gtpase-tc10-modulates-b-cell-immune-responses
#3
Marianne Burbage, Selina J Keppler, Beatriz Montaner, Pieta K Mattila, Facundo D Batista
Rho family GTPases regulate diverse cellular events, such as cell motility, polarity, and vesicle traffic. Although a wealth of data exists on the canonical Rho GTPases RhoA, Rac1, and Cdc42, several other family members remain poorly studied. In B cells, we recently demonstrated a critical role for Cdc42 in plasma cell differentiation. In this study, we focus on a close homolog of Cdc42, TC10 (also known as RhoQ), and investigate its physiological role in B cells. By generating a TC10-deficient mouse model, we show that despite reduced total B cell numbers, B cell development in these mice occurs normally through distinct developmental stages...
July 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28745813/subversion-of-innate-immune-responses-by-francisella-involves-the-disruption-of-traf3-and-traf6-signaling-complexes
#4
Daniela Putzova, Swarupa Panda, Anetta Härtlova, Jiří Stulík, Nelson O Gekara
The success of pathogens depends on their ability to circumvent immune defenses. Francisella tularensis is one of the most infectious bacteria known. The remarkable virulence of Francisella is believed to be due to its capacity to evade or subvert the immune system, but how remains obscure. Here we show that Francisella triggers but concomitantly inhibits the Toll-like receptor (TLR), RIG-I-like receptor (RLR) and Cytoplasmic DNA (CDR) pathways. Francisella subverts these pathways at least in part by inhibiting K63-linked polyubiquitination and assembly of TRAF6 and TRAF3 complexes that control the transcriptional responses of PRRs...
July 26, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28744851/post-translational-regulation-of-antiviral-innate-signaling
#5
REVIEW
Yilong Zhou, Chenxi He, Wang Lin, Baoxue Ge
The innate immune system initiates immune responses by pattern-recognition receptors (PRR). Virus-derived nucleic acids are sensed by the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family and the toll-like receptor (TLR) family as well as the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). These receptors activate IRF3/7 and NF-κB signaling pathways to induce the expression of type I interferons (IFNs) and other cytokines firing antiviral responses within the cell. However, to achieve a favorable outcome for the host, a balanced production of IFNs and activation of antiviral responses is required...
July 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28743964/toll-like-receptor-4-deficiency-reduces-oxidative-stress-and-macrophage-mediated-inflammation-in-hypertensive-kidney
#6
Sathnur Pushpakumar, Lu Ren, Sourav Kundu, Alejandra Gamon, Suresh C Tyagi, Utpal Sen
Oxidative stress and inflammation are integral to hypertension-induced renal injury. A unifying feature for the two components is Toll-like receptors (TLR), which are key regulators of the innate immune system. Recent studies implicate TLR4 activation and oxidative stress in cardiovascular diseases and also as a link between inflammation and hypertension. However, its role in hypertension induced renal injury remains unexplored. In the present study, we investigated whether TLR-4 deficiency reduces Ang-II-induced renal injury and fibrosis by attenuating reactive oxygen species (ROS) production and inflammation...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743632/comparative-analysis-of-dual-specificity-protein-phosphatase-genes-1-2-and-5-in-response-to-immune-challenges-in-japanese-flounder-paralichthys-olivaceus
#7
Shuo Li, Gaixiang Hao, Jiafang Li, Weijiao Peng, Xuyun Geng, Jinsheng Sun
Dual-specificity MAP kinase (MAPK) phosphatases (DUSPs) are well-established negative modulators in regulating MAPK signaling in mammalian cells and tissues. Our previous studies have shown the involvement of DUSP6 in regulating innate immunity in Japanese flounder Paralichthys olivaceus. In order to gain a better understanding of the role of DUSPs in fish innate immunity, in the present study we identified and characterized three additional DUSP genes including DUSP1, 2 and 5 in P. olivaceus. The three Japanese flounder DUSP proteins share common domain structures composed of a conserved N-terminal Rhodanase/CDC25 domain and a C-terminal catalytic phosphatase domain, while they show only less than 26% sequence identities, indicating that they may have different substrate selectivity...
July 22, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28742882/t-cell-intrinsic-tlr2-stimulation-promotes-il-10-expression-and-suppressive-activity-by-cd45rbhi-t-cells
#8
Janice C Jun, Mark B Jones, Douglas M Oswald, Edward S Sim, Amruth R Jonnalagadda, Lori S C Kreisman, Brian A Cobb
While Toll-like receptors (TLRs) represent one of the best characterized innate immune pathways, evidence suggests that TLRs are not restricted to innate leukocytes and some epithelial cells, but are also expressed in T cells. Specifically, published evidence focusing on FoxP3+ regulatory T cells demonstrate that they express functional TLR2, which is already known among the TLR family for its association with immune suppression; however, little is known about the relationship between T cell-intrinsic TLR2 binding and cytokine production, T cell differentiation, or T cell receptor (TCR) stimulation...
2017: PloS One
https://www.readbyqxmd.com/read/28742108/fasting-metabolism-modulates-the-interleukin-12-interleukin-10-cytokine-axis
#9
Johannes J Kovarik, Elisabeth Kernbauer, Markus A Hölzl, Johannes Hofer, Guido A Gualdoni, Klaus G Schmetterer, Fitore Miftari, Yury Sobanov, Anastasia Meshcheryakova, Diana Mechtcheriakova, Nadine Witzeneder, Georg Greiner, Anna Ohradanova-Repic, Petra Waidhofer-Söllner, Marcus D Säemann, Thomas Decker, Gerhard J Zlabinger
A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR), is responsible for controlling the balance between pro-inflammatory interleukin (IL)-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines...
2017: PloS One
https://www.readbyqxmd.com/read/28739303/cpg-oligonucleotides-increase-hbv-specific-cytokine-responses-in-whole-blood-and-enhance-cytokine-release-assay-sensitivity
#10
Werner Dammermann, Julia Dornbrack, Katharina Bröker, Frank Bentzien, Stefan Lüth
BACKGROUND: Chronic hepatitis B leads to liver cirrhosis and hepatocellular carcinoma. To develop a therapeutic vaccine for chronic hepatitis B patients it is necessary to assess cellular immune responses to hepatitis B virus(HBV) antigens. We investigated the potential of toll-like receptor(TLR) 9 agonists, i.e. CpG oligonucleotides, as costimulators to increase diagnostic sensitivity and specificity of our HBV specific cytokine release assay. METHODS: Whole blood from 80 healthy individuals(n=51 hepatitis B vaccinated, n=29 unvaccinated) was stimulated with hepatitis B surface antigen(HBsAg) or hepatitis B core antigen(HBcAg) in presence or absence of CpG oligonucleotides...
July 21, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28739292/a-polar-sxxs-motif-drives-assembly-of-the-transmembrane-domains-of-toll-like-receptor-4
#11
Vasileios Kargas, Jan K Marzinek, Daniel A Holdbrook, Hang Yin, Robert C Ford, Peter J Bond
Like all members of the Toll-like receptor (TLR) family, TLR4 comprises of a large ectodomain (ECD) involved in ligand recognition at the cell-surface, and a cytosolic Toll/interleukin-1 receptor (TIR) signalling domain, linked by a lipid membrane-anchored transmembrane (TM) domain (TMD). Binding of immunostimulatory pathogen-associated molecular patterns (PAMPs) such as bacterial lipopolysaccharide (LPS) to myeloid differentiation factor 2 (MD-2) coreceptor-complexed TLR4 leads to its dimerization, resulting in productive juxtaposition of TIR domains and the initiation of pro-inflammatory innate immune responses...
July 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28736945/tim-1-b-cells-suppress-t-cell-interferon-gamma-production-and-promote-foxp3-expression-but-have-impaired-regulatory-function-in-coronary-artery-disease
#12
Xiao-Long Gu, Huan He, Lin Lin, Guo-Xin Luo, Yan-Fei Wen, Ding-Cheng Xiang, Jian Qiu
Atherosclerosis and its associated coronary artery disease (CAD) represent another chronic low-grade inflammatory disorder. Regulatory B cells (Bregs) possess essential functions in maintaining peripheral tolerance and inhibiting pathogenic inflammation through IL-10. Here, we investigated one subset of Bregs, Tim-1(+) B cell, and its role in atherosclerosis and CAD patients. In healthy individuals, IL-10-producing B cells were predominantly found in the Tim-1(+) B cells. Upon stimulation of the B cell receptor (BCR) and Toll-like receptor 9 (TLR-9) by anti-BCR antibodies and CpG, respectively, the Tim-1(+) B cells could further upregulate IL-10 expression...
July 24, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28736159/a-novel-ccr-2-tlr-2-triggered-signaling-in-murine-peritoneal-macrophages-intensifies-bacterial-staphylococcus-aureus-killing-by-reactive-oxygen-species-through-tnf-r1
#13
Ajeya Nandi, Biswadev Bishayi
Macrophages are remarkably versatile in their ability to recognize and respond to a wide range of stimuli by expressing a variety of surface and intracellular receptors and triggering multiple signal transduction pathways. The onset of microbial infection is primarily determined by the initial contacts made by the microbes with the host macrophages. Although there prevail a relationship between the chemokine receptor and Toll like receptors during disease, particularly TLR-2 and CCR-2 signaling interdependence on each other has not been yet investigated during acute staphylococcal infection...
July 20, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28735358/il-10-and-tgf-%C3%AE-unbalanced-levels-in-neutrophils-contribute-to-increase-inflammatory-cytokine-expression-in-childhood-obesity
#14
Nayara I Medeiros, Rafael T Mattos, Carlos A Menezes, Rafaelle C G Fares, André Talvani, Walderez O Dutra, Fabrício Rios-Santos, Rodrigo Correa-Oliveira, Juliana A S Gomes
PURPOSE: Obesity is a multifactorial disease, associated with metabolic disorders, chronic low-grade inflammation, and impaired immunity. This study aimed to evaluate the childhood obesity-associated effects on neutrophil activation and cytokine production. METHODS: We evaluated activation and recognition markers and cytokine production in neutrophils from the peripheral blood of children with obesity and normal weight using multicolor flow cytometry. RESULTS: We demonstrate a higher frequency of neutrophils in childhood obesity group (CO) compared to normal-weight group (NW)...
July 22, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28734965/enhanced-immunostimulatory-activity-of-in-silico-discovered-agonists-of-toll-like-receptor-2-tlr2
#15
M S Murgueitio, S Ebner, P Hörtnagl, C Rakers, R Bruckner, P Henneke, G Wolber, S Santos-Sierra
BACKGROUND: Emergent therapies in anticancer vaccination use Toll-like receptors (TLRs) agonists as dendritic cell (DC) vaccine adjuvants. DCs from the patient are isolated, stimulated with TLR agonists and tumor antigens ex vivo and then infused back into the patient. Although some TLR ligands have been tested in clinical trials, novel TLR agonists with improved immunomodulatory properties are essential to optimize treatment success. We report on the discovery of small-molecule TLR2 agonists, with favorable properties as synthetic adjuvants...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28733487/the-stat4-mll1-epigenetic-axis-regulates-the-antimicrobial-functions-of-murine-macrophages
#16
William F Carson, Karen A Cavassani, Elyara M Soares, Soichiro Hirai, Nicolai A Kittan, Matthew A Schaller, Melissa M Scola, Amrita Joshi, Akihiro Matsukawa, David M Aronoff, Craig N Johnson, Yali Dou, Katherine A Gallagher, Steven L Kunkel
Macrophages are critical immune cells for the clearance of microbial pathogens and cellular debris from peripheral tissues. Macrophage inflammatory responses are governed by gene expression patterns, and these patterns are often subject to epigenetic control. Chromatin modifications, such as histone methylation, regulate gene accessibility in macrophages, and macrophage polarization is governed in part by the expression and function of chromatin-modifying enzymes. The histone methyltransferase mixed-lineage leukemia 1 (MLL1) preferentially modifies lysine residue 4 on the unstructured protein tail of histone H3...
July 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28730622/susceptibility-to-hiv-1-infection-is-influenced-by-toll-like-receptor-2-196-to-174-polymorphism-in-north-indian-population
#17
Sanjukta Vidyant, Animesh Chatterjee, Vikas Agarwal, Tapan N Dhole
INTRODUCTION: Toll like receptors (TLRs) are pattern recognition receptors, recognize molecular patterns of pathogens and play an important role in innate immunity. Recent studies have identified that single nucleotide polymorphism (SNPs) in TLR gene impairs the response to TLR ligands in some individuals and is associated with susceptibility to various infectious diseases. AIM: The aim of the present study is to investigate the role of four SNPs in the TLR2 gene, -196 to -174 Ins/Del, 2258 G/A (Arg753Gln), 2029 C/T (Arg677Trp) and 1892 C/A (Pro631His) with susceptibility and progression to HIV-1 in North Indian individuals...
July 20, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28730487/a-methodology-for-comprehensive-analysis-of-toll-like-receptor-signaling-in-macrophages
#18
Marijke Koppenol-Raab, Aleksandra Nita-Lazar
A combination of high-throughput, multiplexed, quantitative methods with computational modeling and statistical approaches is required to obtain system-level understanding of biological function. Mass spectrometry (MS)-based proteomics has emerged as a preferred tool for the analysis of changes in protein abundance and their post-translational modification (PTM) levels at a global scale, comparable with genomic experiments and generating data suitable for use in mathematical modeling of signaling pathways. Here we describe a set of parallel bottom-up proteomic approaches to detect and quantify the global protein changes in total intracellular proteins, their phosphorylation, and the proteins released by active and passive secretion or shedding mechanisms (referred to as the secretome as reviewed in Makridakis and Vlahou, J Proteome 73:2291-2305, 2010) in response to the stimulation of Toll-like receptors (TLRs) with specific ligands in cultured macrophages...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730145/prokaryotic-rna-associated-to-bacterial-viability-induces-polymorphonuclear-neutrophil-activation
#19
Nahuel Rodriguez-Rodrigues, Luis A Castillo, Verónica I Landoni, Daiana Martire-Greco, M Ayelén Milillo, Paula Barrionuevo, Gabriela C Fernández
Polymorphonuclear neutrophils (PMN) are the first cellular line of antibacterial host defense. They sense pathogens through recognition of pathogen-associated molecular patterns (PAMPs) by innate pattern recognition receptors, such as Toll-like receptors (TLR). The aim of this study was to investigate whether PMN sense bacterial viability and explore which viability factor could be involved in this phenomenon. For this purpose, different functions were evaluated in isolated human PMN using live Escherichia coli (Ec) and heat-killed Ec (HK-Ec)...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28729359/the-%C3%AE-defensin-retrocyclin-101-inhibits-tlr4-and-tlr2-dependent-signaling-and-protects-mice-against-influenza-infection
#20
Daniel Prantner, Kari Ann Shirey, Wendy Lai, Wuyuan Lu, Alexander M Cole, Stefanie N Vogel, Alfredo Garzino-Demo
Despite widespread use of annual influenza vaccines, seasonal influenza-associated deaths number in the thousands each year, in part because of exacerbating bacterial superinfections. Therefore, discovering additional therapeutic options would be a valuable aid to public health. Recently, TLR4 inhibition has emerged as a possible mechanism for protection against influenza-associated lethality and acute lung injury. Based on recent data showing that rhesus macaque θ-defensins could inhibit TLR4-dependent gene expression, we tested the hypothesis that a novel θ-defensin, retrocyclin (RC)-101, could disrupt TLR4-dependent signaling and protect against viral infection...
July 20, 2017: Journal of Leukocyte Biology
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