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https://www.readbyqxmd.com/read/28182609/genetic-polymorphisms-associated-with-liver-disease-progression-in-hiv-hcv-coinfected-patients
#1
Luz M Medrano, María A Jiménez-Sousa, Amanda Fernández-Rodríguez, Salvador Resino
The pathogenic mechanisms of the accelerated progression of liver injury in HIV/HCV coinfection are incompletely understood. The progression of liver disease is variable between individuals having similar risk factors, suggesting that genetic background is an important contributor. The aim of this review is to give a summary of all single nucleotide polymorphisms associated with the severity of liver disease in patients coinfected with HIV and HCV reported in the literature. Therefore, a systematic search for articles published was made, 17 of which were selected for this review...
January 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28159900/serum-mir-29a-is-upregulated-in-acute-graft-versus-host-disease-and-activates-dendritic-cells-through-tlr-binding
#2
Parvathi Ranganathan, Apollinaire Ngankeu, Nina C Zitzer, PierPaolo Leoncini, Xueyan Yu, Lucia Casadei, Kishore Challagundla, Dawn K Reichenbach, Sabrina Garman, Amy S Ruppert, Stefano Volinia, Jessica Hofstetter, Yvonne A Efebera, Steven M Devine, Bruce R Blazar, Muller Fabbri, Ramiro Garzon
Acute graft-versus-host disease (aGVHD) continues to be a frequent and devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT), posing as a significant barrier against the widespread use of HSCTs as a curative modality. Recent studies suggested serum/plasma microRNAs (miRs) may predict aGVHD onset. However, little is known about the functional role of circulating miRs in aGVHD. In this article, we show in two independent cohorts that miR-29a expression is significantly upregulated in the serum of allogeneic HSCT patients at aGVHD onset compared with non-aGVHD patients...
February 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28146629/identification-of-high-potency-human-tlr8-and-dual-tlr7-tlr8-agonists-in-pyrimidine-2-4-diamines
#3
Mallesh Beesu, Alex C D Salyer, Michael J H Brush, Kathryn L Trautman, Justin K Hill, Sunil A David
The induction of Toll-like receptor 7 (TLR7)-dependent Type I interferons (IFN-α/β) from plasmacytoid dendritic cells as well as the production of TLR8-dependent Type II interferon (IFN-γ), TNF-α, and IL-12 in myeloid dendritic cells are of importance in generating T helper-1 biased adaptive immune responses. In an effort to identify novel dual TLR7/TLR8-active compounds, we undertook structure-activity relationship studies in pyrimidine 2,4-diamines, focusing on substituents at C5. Several analogues substituted with aminopropyl appendages at C5 displayed dominant TLR8-agonistic activity...
February 1, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28125903/bone-marrow-cd34-progenitor-cells-from-hiv-infected-patients-show-an-impaired-t-cell-differentiation-potential-related-to-pro-inflammatory-cytokines
#4
Veronica Bordoni, Michele Bibas, Domenico Viola, Alessandra Sacchi, Eleonora Cimini, Nicola Tumino, Rita Casetti, Alessandra Amendola, Adriana Ammassari, Chiara Agrati, Federico Martini
The impact of HIV infection on the frequency and differentiation capability of CD34+ Bone Marrow Hematopoietic Progenitor Cells (BM-HPCs) is still debated, having a possible primary role in antiretroviral-induced immunoreconstitution. We investigated the influence of HIV replication or pro-inflammatory cytokines on lymphopoietic capability of BM-HPCs from 7 viremic (VR) and 5 non-viremic (NVR) HIV infected patients. We found that BM-HPCs from VR patients were unable to differentiate in vitro toward T cells, and produced pro-inflammatory cytokines in the absence of viral replication...
January 26, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28122964/circulating-and-exosome-packaged-hepatitis-c-single-stranded-rna-induce-monocyte-differentiation-via-tlr7-8-to-polarized-macrophages-and-fibrocytes
#5
Banishree Saha, Karen Kodys, Adeyinka Adejumo, Gyongyi Szabo
Monocytes and macrophages (MΦs) play a central role in the pathogenesis of chronic hepatitis C virus (HCV) infection. The tissue microenvironment triggers monocyte differentiation into MΦs, with polarization ranging within the spectrum of M1 (classical) to M2 (alternative) activation. Recently, we demonstrated that HCV infection leads to monocyte differentiation into polarized MΦs that mediate stellate cell activation via TGF-β. In this study, we aimed to identify the viral factor(s) that mediate monocyte-to-MΦ differentiation...
January 25, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28069966/inherited-human-irak-1-deficiency-selectively-impairs-tlr-signaling-in-fibroblasts
#6
Erika Della Mina, Alessandro Borghesi, Hao Zhou, Salim Bougarn, Sabri Boughorbel, Laura Israel, Ilaria Meloni, Maya Chrabieh, Yun Ling, Yuval Itan, Alessandra Renieri, Iolanda Mazzucchelli, Sabrina Basso, Piero Pavone, Raffaele Falsaperla, Roberto Ciccone, Rosa Maria Cerbo, Mauro Stronati, Capucine Picard, Orsetta Zuffardi, Laurent Abel, Damien Chaussabel, Nico Marr, Xiaoxia Li, Jean-Laurent Casanova, Anne Puel
Most members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) families transduce signals via a canonical pathway involving the MyD88 adapter and the interleukin-1 receptor-associated kinase (IRAK) complex. This complex contains four molecules, including at least two (IRAK-1 and IRAK-4) active kinases. In mice and humans, deficiencies of IRAK-4 or MyD88 abolish most TLR (except for TLR3 and some TLR4) and IL-1R signaling in both leukocytes and fibroblasts. TLR and IL-1R responses are weak but not abolished in mice lacking IRAK-1, whereas the role of IRAK-1 in humans remains unclear...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28062211/endosomal-toll-like-receptor-gene-polymorphisms-and-susceptibility-to-hiv-and-hcv-co-infection-differential-influence-in-individuals-with-distinct-ethnic-background
#7
Jacqueline M Valverde-Villegas, Bruno Paiva Dos Santos, Rúbia Marília de Medeiros, Vanessa Suñé Mattevi, Rosmeri Kuhmmer Lazzaretti, Eduardo Sprinz, Regina Kuhmmer, José Artur Bogo Chies
The genetic background of human populations can influence the susceptibility and outcome of infection diseases. Toll-like receptors (TLRs) have been previously associated with susceptibility to human immunodeficiency virus (HIV) infection, disease progression and hepatitis C, virus (HCV) co-infection in different populations, although mostly in Europeans. In this study, we investigated the genetic role of endosomal TLRs on susceptibility to HIV infection and HCV co-infection through the analysis of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and TLR9 rs352140 polymorphisms in 789 Brazilian individuals (374 HIV+ and 415 HIV-), taking into account their ethnic background...
January 4, 2017: Human Immunology
https://www.readbyqxmd.com/read/28049494/adjuvant-effects-of-a-sequence-engineered-mrna-vaccine-translational-profiling-demonstrates-similar-human-and-murine-innate-response
#8
Darin K Edwards, Edith Jasny, Heesik Yoon, Nigel Horscroft, Brian Schanen, Tanya Geter, Mariola Fotin-Mleczek, Benjamin Petsch, Vaughan Wittman
BACKGROUND: Prophylactic and therapeutic vaccines often depend upon a strong activation of the innate immune system to drive a potent adaptive immune response, often mediated by a strong adjuvant. For a number of adjuvants immunological readouts may not be consistent across species. METHODS: In this study, we evaluated the innate immunostimulatory potential of mRNA vaccines in both humans and mice, using a novel mRNA-based vaccine encoding influenza A hemagglutinin of the pandemic strain H1N1pdm09 as a model...
January 3, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28039018/estrogen-regulated-stat1-activation-promotes-tlr8-expression-to-facilitate-signaling-via-microrna-21-in-systemic-lupus-erythematosus
#9
Nicholas A Young, Giancarlo R Valiente, Jeffrey M Hampton, Lai-Chu Wu, Craig J Burd, William L Willis, Michael Bruss, Holly Steigelman, Maya Gotsatsenko, Stephanie A Amici, Mary Severin, Lucila Marino Claverie, Mireia Guerau-de-Arellano, Amy Lovett-Racke, Stacy Ardoin, Wael N Jarjour
Recent studies implicate innate immunity to systemic lupus erythematosus (SLE) pathogenesis. Toll-like receptor (TLR)8 is estrogen-regulated and binds viral ssRNA to stimulate innate immune responses, but recent work indicates that microRNA (miR)-21 within extracellular vesicles (EVs) can also trigger this receptor. Our objective was to examine TLR8 expression/activation to better understand sex-biased responses involving TLR8 in SLE. Our data identify an estrogen response element that promotes STAT1 expression and demonstrate STAT1-dependent transcriptional activation of TLR8 with estrogen stimulation...
December 27, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28028829/localization-of-nucleic-acid-sensing-toll-like-receptors-in-human-and-mouse-pancreas
#10
Olli Helminen, Heikki Huhta, Joonas H Kauppila, Petri P Lehenkari, Juha Saarnio, Tuomo J Karttunen
Nucleic acid-sensing toll-like receptors (TLRs) (3, 7, 8, 9) have a role both in antiviral innate immunity and in autoimmune disorders. We assessed the expression of TLR3, 7, 8 and 9 in human and mouse pancreas focusing on the subpopulations of cells in the Langerhans islets. We studied eight human samples with normal pancreatic islets and two samples from patients with type 1 diabetes. Additionally, 10 CD-1 mouse pancreases were analysed. Immunohistochemical double-stainings for the TLRs and insulin, glucagon or somatostatin, respectively, were performed along with appropriate controls...
February 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28027081/altered-expression-of-toll-like-receptors-in-human-oral-epithelium-in-oral-lichenoid-reactions
#11
Abdelhakim Salem, Rabeia Mustafa, Dyah Listyarifah, Ahmed Al-Samadi, Goncalo Barreto, Dan Nordström, Kari K Eklund
Oral lichenoid reactions (OLRs) are chronic inflammatory lesions induced by contact with allergens. Toll-like receptors (TLRs) are members of pattern-recognition receptor superfamily. Once activated, TLRs induce production of cytokines and chemokines, thus leading to inflammatory reaction in host tissue. In the present study, we aimed to investigate the potential role of TLRs in the initiation and perpetuation of OLRs, in which TLRs induce innate immune responses mounted against allergens. TLRs, 1 through 10, were mapped in tissue samples obtained from healthy donors and OLR patients using real-time quantitative reverse transcription polymerase chain reaction, immunostaining, and image analyses...
December 23, 2016: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28017496/toll-like-receptor-3-and-interferon-%C3%AE-mrna-expressions-were-increased-in-peripheral-blood-of-ischemic-stroke-patients-with-good-outcome
#12
Lingna Deng, Jingrui Pan, Qingxia Peng, Zhaofei Dong, Yidong Wang
BACKGROUND: Innate immunity plays an important role in brain ischemic injury, but there are only few studies on the effects of toll-like receptors (TLRs) on cerebral infarction patients up to now. We aimed to evaluate the TLR mRNA expression of patients with different outcomes. METHODS: Eighty-six cases suffering from cerebral infarction within 14 days were assigned into the good outcome group (n = 47) and the bad outcome group (n = 39) depending on the modified Rankin Scale scores (mRS ≤2 at 90 days following stroke onset was good outcome)...
December 22, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28013457/selective-evolution-of-toll-like-receptors-3-7-8-and-9-in-bats
#13
Haiying Jiang, Juan Li, Linmiao Li, Xiujuan Zhang, Lihong Yuan, Jinping Chen
Previous studies have shown that bats are reservoirs of a large number of viruses, many of which cause illness and mortality in humans and other animals. However, these bat-associated pathogens cause little, if any, clinicopathology in bats. This long-term adaptation should be reflected somewhat in the immune system. Toll-like receptors (TLRs) are the first line of immune defense against pathogens in vertebrates. Therefore, this study focuses on the selection of TLRs involved in virus recognition. The coding sequences of TLR3, TLR7, TLR8, and TLR9 were sequenced in ten bats...
December 24, 2016: Immunogenetics
https://www.readbyqxmd.com/read/28002600/differential-expression-of-toll-like-receptors-in-goat-dominant-and-nondominant-follicles
#14
G X E, Y J Zhao, Y H Ma, M X Chu, Q H Hong, S J Lv, L Zhu, F K Li, Y G Han, X Wu, Y F Huang
The mechanism of dominant follicle selection is unclear because of its physiological complexity. However, some studies have reported that the immune system plays an important role in reproductive physiology. The objective of the current study was to investigate the differential expression of Toll-like receptors (TLRs) in the dominant (DFs) and nondominant follicles (NFs), and to determine the correlation between the expression of TLRs and the related genes, such as WNT4 and FOXL2. In this comparative study, the expression levels of TLRs, WNT4, and FOXL2 genes of DFs and NFs were obtained from three Dazu black goats were estimated using the real-time PCR...
December 19, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27997520/polymorphisms-of-mannose-binding-lectin-and-toll-like-receptors-2-3-4-7-and-8-and-the-risk-of-respiratory-infections-and-acute-otitis-media-in-children
#15
Laura Toivonen, Juho Vuononvirta, Jussi Mertsola, Matti Waris, Qiushui He, Ville Peltola
BACKGROUND: Mannose-binding lectin (MBL) and toll-like receptors (TLR) are important components of the innate immune system. We assessed the susceptibility of children with genetic variants in these factors to respiratory infections, rhinovirus infections, and acute otitis media. METHODS: In a prospective cohort study, blood samples from 381 Finnish children were analyzed for polymorphisms in MBL2 at codons 52, 54, and 57, TLR2 Arg753Gln, TLR3 Leu412Phe, TLR4 Asp299Gly, TLR7 Gln11Leu, and TLR8 Leu651Leu...
December 15, 2016: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/27943374/expression-of-toll-like-receptors-in-peripheral-blood-mononuclear-cells-of-patients-with-primary-sj%C3%A3-gren-s-syndrome
#16
Marie Karlsen, Kjerstin Jakobsen, Roland Jonsson, Daniel Hammenfors, Torbjørn Hansen, Silke Appel
Toll-like receptors (TLR) are pattern-recognition receptors important for the detection of pathogen-associated molecular patterns. They are localized on cellular membranes, either on the cell surface or the endosomes. Primary Sjögren's syndrome (pSS) is a systemic rheumatic autoimmune disease characterized by lymphocytic infiltrations in exocrine glands resulting in dry eyes and mouth. In a majority of patients, autoantibodies against Ro/SSA and/or La/SSB are present. Here we analyzed mRNA levels of TLR1-10 and protein expression levels of most of them in human peripheral blood mononuclear cells from 20 pSS patients and 20 healthy controls...
December 10, 2016: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/27928016/promising-role-of-toll-like-receptor-8-agonist-in-concert-with-prostratin-for-activation-of-silent-hiv
#17
M A Rochat, E Schlaepfer, R F Speck
: The persistence of latently HIV-infected cells in patients under combined antiretroviral treatment (cART) remains the major hurdle for HIV eradication. Thus far, individual compounds have not been sufficiently potent to reactivate latent virus and guarantee its elimination in vivo. Thus, we hypothesized that transcriptional enhancers, in concert with compounds triggering the innate immune system, are more efficient in reversing latency by creating a Th1 supportive milieu that acts against latently HIV-infected cells at various levels...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27810904/phase-1b-trial-of-the-toll-like-receptor-8-agonist-motolimod-vtx-2337-combined-with-cetuximab-in-patients-with-recurrent-or-metastatic-scchn
#18
Laura Q M Chow, Chihiro Morishima, Keith D Eaton, Christina S Baik, Bernardo H Goulart, Leslie N Anderson, Kristi L Manjarrez, Gregory N Dietsch, James Kyle Bryan, Robert M Hershberg, Mary L Disis, Renato G Martins
PURPOSE: As toll-like receptors (TLRs) are key mediators of immune responses, TLR agonists may be important for augmenting the efficacy of therapies for squamous cell carcinoma of the head and neck (SCCHN). Motolimod (VTX-2337), a selective small-molecule agonist of TLR8, stimulates NK cells, dendritic cells, and monocytes. A Phase 1b clinical trial assessed the safety and anti-tumor activity of motolimod in combination with cetuximab in patients with SCCHN. Correlative biomarkers of immune activity were explored...
November 3, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27798161/tlr8-couples-socs-1-and-restrains-tlr7-mediated-antiviral-immunity-exacerbating-west-nile-virus-infection-in-mice
#19
Amber M Paul, Dhiraj Acharya, Linda Le, Penghua Wang, Dobrivoje S Stokic, A Arturo Leis, Lena Alexopoulou, Terrence Town, Richard A Flavell, Erol Fikrig, Fengwei Bai
West Nile virus (WNV) is a neurotropic ssRNA flavivirus that can cause encephalitis, meningitis, and death in humans and mice. Human TLR7 and TLR8 and mouse TLR7 recognize viral ssRNA motifs and induce antiviral immunity. However, the role of mouse TLR8 in antiviral immunity is poorly understood. In this article, we report that TLR8-deficient (Tlr8(-/-)) mice were resistant to WNV infection compared with wild-type controls. Efficient WNV clearance and moderate susceptibility to WNV-mediated neuronal death in Tlr8(-/-) mice were attributed to overexpression of Tlr7 and IFN-stimulated gene-56 expression, whereas reduced expression of the proapoptotic gene coding Bcl2-associated X protein was observed...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27798148/rage-enhances-tlr-responses-through-binding-and-internalization-of-rna
#20
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
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