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https://www.readbyqxmd.com/read/29331320/zika-dengue-and-yellow-fever-viruses-induce-differential-anti-viral-immune-responses-in-human-monocytic-and-first-trimester-trophoblast-cells
#1
Huanle Luo, Evandro R Winkelmann, Ildefonso Fernandez-Salas, Li Li, Sandra V Mayer, Rogelio Daniz-Lozano, Rosa Ma Sanchez-Casas, Nikos Vasilakis, Robert Tesh, Alan D Barrett, Scott C Weaver, Tian Wang
Zika virus (ZIKV) is a mosquito-borne flavivirus associated with severe neonatal birth defects, but the causative mechanism is incompletely understood. ZIKV shares sequence homology and early clinical manifestations with yellow fever virus (YFV) and dengue virus (DENV) and are all transmitted in urban cycles by the same species of mosquitoes. However, YFV and DENV have been rarely reported to cause congenital diseases. Here, we compared infection with a contemporary ZIKV strain (FSS13025) to YFV17D and DENV-4 in human monocytic cells (THP-1) and first-trimester trophoblasts (HTR-8)...
January 10, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29321259/plasmacytoid-dendritic-cells-promote-systemic-sclerosis-with-a-key-role-for-tlr8
#2
Marie Dominique Ah Kioon, Claudio Tripodo, David Fernandez, Kyriakos A Kirou, Robert F Spiera, Mary K Crow, Jessica K Gordon, Franck J Barrat
Systemic sclerosis (SSc) is a multisystem life-threatening fibrosing disorder that lacks effective treatment. The link between the inflammation observed in organs such as the skin and profibrotic mechanisms is not well understood. The plasmacytoid dendritic cell (pDC) is a key cell type mediating Toll-like receptor (TLR)-induced inflammation in autoimmune disease patients, including lupus and skin diseases with interface dermatitis. However, the role of pDCs in fibrosis is less clear. We show that pDCs infiltrate the skin of SSc patients and are chronically activated, leading to secretion of interferon-α (IFN-α) and CXCL4, which are both hallmarks of the disease...
January 10, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29241030/expression-profiles-of-genes-involved-in-tlrs-and-nlrs-signaling-pathways-of-water-buffaloes-infected-with-fasciola-gigantica
#3
Fu-Kai Zhang, Jun-Ling Hou, Ai-Jiang Guo, Ai-Ling Tian, Zhao-An Sheng, Wen-Bin Zheng, Wei-Yi Huang, Hany M Elsheikha, Xing-Quan Zhu
Infection of ruminants and humans with Fasciola gigantica is attracting increasing attention due to its economic impact and public health significance. However, little is known of innate immune responses during F. gigantica infection. Here, we investigated the expression profiles of genes involved in Toll-like receptors (TLRs) and NOD-like receptors (NLRs) signaling pathways in buffaloes infected with 500F. gigantica metacercariae. Serum, liver and peripheral blood mononuclear cell (PBMC) samples were collected from infected and control buffaloes at 3, 10, 28, and 70days post infection (dpi)...
December 11, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29196629/immune-and-imaging-correlates-of-mild-cognitive-impairment-conversion-to-alzheimer-s-disease
#4
Francesca La Rosa, Marina Saresella, Francesca Baglio, Federica Piancone, Ivana Marventano, Elena Calabrese, Raffaello Nemni, Enrico Ripamonti, Monia Cabinio, Mario Clerici
Amnestic mild cognitive impairment (aMCI) conversion to Alzheimer's disease (AD) is seen in a sizable portion of aMCI patients; correlates predicting such conversion are poorly defined but neuroinflammation and the reactivation of chronic viral infections are suspected to play a role in this phenomenon. We analyzed these aspects in two homogeneous groups of aMCI who did or did not convert to AD over a 24-months period. Results showed that at baseline in those aMCI individuals who did not convert to AD: 1) Aβ1-42 stimulated production of the pro-inflammatory cytokines IL6 and IL1β by CD14+ cells was significantly reduced (p = 0...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29190907/profile-of-differentially-expressed-toll-like-receptor-signaling-genes-in-the-natural-killer-cells-of-patients-with-s%C3%A3-zary-syndrome
#5
Kelly C G ManfrereC, Marina P Torrealba, Denis R Miyashiro, Nátalli Z Pereira, Fabio S Y Yoshikawa, Luana de M Oliveira, Jade Cury-Martins, Alberto J S Duarte, José A Sanches, Maria N Sato
Sézary syndrome (SS), an aggressive and leukemic form of cutaneous T-cell lymphoma, usually results in shortened survival. Improving innate immunity in SS by targeting natural killer (NK) cells with Toll-like receptor (TLR) agonists could be an interesting modulatory strategy. We evaluated the NK cell populations in SS patients assessing activating and inhibitory receptors expression and profiled the differential expression of TLR signaling pathway genes in unstimulated NK cells and after TLR7/8 stimulation...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29181003/the-human-associated-archaeon-methanosphaera-stadtmanae-is-recognized-through-its-rna-and-induces-tlr8-dependent-nlrp3-inflammasome-activation
#6
Tim Vierbuchen, Corinna Bang, Hanna Rosigkeit, Ruth A Schmitz, Holger Heine
The archaeon Methanosphaera stadtmanae is a member of the gut microbiota; yet, the molecular cross-talk between archaea and the human immune system and its potential contribution to inflammatory diseases has not been evaluated. Although archaea are as bacteria prokaryotes, they form a distinct domain having unique features such as different cell wall structures and membrane lipids. So far, no microbe-associated molecular patterns of archaea which activate innate immune receptors have been identified. By stimulating human myeloid cells with M...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29174509/tlr8-activation-and-inhibition-by-guanosine-analogs-in-rna-importance-of-functional-groups-and-chain-length
#7
Tiannan Hu, Scott R Suter, Madeline M Mumbleau, Peter A Beal
Toll-like receptor 8 (TLR8) is an important component of the human innate immune system that recognizes single stranded RNA (ssRNA). Recent X-ray crystal structures of TLR8 bound to ssRNA revealed a previously unrecognized binding site for a 5'-UpG-3' dinucleotide. Here we use an atomic mutagenesis strategy coupled with a cellular TLR8 activation assay to probe the importance of specific functional groups present on the guanine base in RNA-mediated receptor agonism and antagonism. Results from RNA analogs containing 7-deazaguanosine, 2-aminopurine and inosine confirm the importance of guanine N7, O6 and N2, respectively, in TLR8 activation...
November 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29155428/small-molecule-inhibition-of-tlr8-through-stabilization-of-its-resting-state
#8
Shuting Zhang, Zhenyi Hu, Hiromi Tanji, Shuangshuang Jiang, Nabanita Das, Jing Li, Kentaro Sakaniwa, Jin Jin, Yanyan Bian, Umeharu Ohto, Toshiyuki Shimizu, Hang Yin
Endosomal Toll-like receptors (TLR3, TLR7, TLR8, and TLR9) are highly analogous sensors for various viral or bacterial RNA and DNA molecular patterns. Nonetheless, few small molecules can selectively modulate these TLRs. In this manuscript, we identified the first human TLR8-specific small-molecule antagonists via a novel inhibition mechanism. Crystal structures of two distinct TLR8-ligand complexes validated a unique binding site on the protein-protein interface of the TLR8 homodimer. Upon binding to this new site, the small-molecule ligands stabilize the preformed TLR8 dimer in its resting state, preventing activation...
November 20, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29152559/fasciola-hepatica-esps-could-indistinctly-activate-or-block-multiple-toll-like-receptors-in-a-human-monocyte-cell-line
#9
Olgary Figueroa-Santiago, Ana M Espino
Fasciola hepatica is a parasitic helminth that induces Th2/Treg responses in its mammalian host. Some reports have suggested that ESPs achieve these polarized immune responses by delaying the activation of dendritic cells and macrophages during the early stages of innate immunity, a process that is mediated by TLR4. The present study aimed to investigate whether TLRs other than TLR4 could also be targeted by F. hepatica ESPs. To achieve this aim a screening system was optimized using THP1-Blue CD14 cells. ESPs were first separated based on their molecular weight and according their net charge by ion exchange chromatography (IEC)...
2017: Annals of Clinical Pathology
https://www.readbyqxmd.com/read/29152046/design-and-synthesis-of-n1-modified-imidazoquinoline-agonists-for-selective-activation-of-toll-like-receptors-7-and-8
#10
Peter Larson, Tamara A Kucaba, Zhengming Xiong, Michael Olin, Thomas S Griffith, David M Ferguson
A series of N1-modified imidazoquinolines were synthesized and screened for Toll-like receptors (TLR) 7 and 8 activities to identify recognition elements that confer high affinity binding and selectivity. These receptors are key targets in the development of immunomodulatory agents that signal the NF-κB mediated transcription of pro-inflammatory chemokines and cytokines. Results are presented showing both TLR7/8 activations are highly correlated to N1-substitution, with TLR8 selectivity achieved through inclusion of an ethyl-, propyl-, or butylamino group at this position...
November 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29133347/analysis-of-the-human-mucosal-response-to-cholera-reveals-sustained-activation-of-innate-immune-signaling-pathways
#11
Daniel L Bourque, Taufiqur Rahman Bhuiyan, Diane P Genereux, Rasheduzzaman Rashu, Crystal N Ellis, Fahima Chowdhury, Ashraful I Khan, Nur Haq Alam, Anik Paul Lazina Hossain, Leslie M Mayo-Smith, Richelle C Charles, Ana A Weil, Regina C LaRocque, Stephen B Calderwood, Edward T Ryan, Elinor K Karlsson, Firdausi Qadri, Jason B Harris
To better understand the innate immune response to Vibrio cholerae infection, we tracked gene expression in the duodenal mucosa of eleven Bangladeshi adults with cholera, using biopsies obtained immediately after rehydration and at 30 and 180 days later. We identified differentially expressed genes and performed an analysis to predict differentially regulated pathways and upstream regulators. During acute cholera, there was a broad increase in the expression of genes associated with innate immunity, including activation of the NF-κB, MAPK, and TLR-mediated signaling pathways, which unexpectedly persisted even 30 days after infection...
November 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29128662/activation-of-innate-immunity-in-primary-human-cells-using-a-plant-virus-derived-nanoparticle-tlr7-8-agonist
#12
Damien Carignan, Sabine Herblot, Marie-Ève Laliberté-Gagné, Marilène Bolduc, Michel Duval, Pierre Savard, Denis Leclerc
Rod-shaped virus-like nanoparticles (VLNP) made of papaya mosaic virus (PapMV) coat proteins (CP) self-assembled around a single stranded RNA (ssRNA) were showed to be a TLR7 agonist. Their utilization as an immune modulator in cancer immunotherapy was shown to be promising. To establish a clinical relevance in human for PapMV VLNP, we showed that stimulation of human peripheral blood mononuclear cells (PBMC) with VLNP induces the secretion of interferon alpha (IFNα) and other pro-inflammatory cytokines and chemokines...
November 8, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29103998/tlr8-combined-withtlr3-or-tlr4-agonists-enhances-dc-nk-driven-effector-tc1-cells
#13
Mahyar Nouri-Shirazi, Saba Tamjidi, Erika Nourishirazi, Elisabeth Guinet
BACKGROUND: Most current prophylactic vaccines confer protection primarily through humoral immunity. Indeed, aluminum salts which have been widely used as adjuvants in vaccines primarily enhance Th2-driven antibody responses. Therefore, new vaccines formulation is moving toward a careful selection of adjuvants that also elicit significant Th1 or Tc1 responses. Several TLR agonists have been tested as potential new adjuvants in clinical and preclinical studies with some efficacy. These studies suggest that combining more than one of TLR ligands enhances the magnitude of immune responses to cancer and infectious disease...
November 2, 2017: Immunology Letters
https://www.readbyqxmd.com/read/29095429/activation-of-toll-like-receptors-in-meconium-aspiration-syndrome
#14
V Anand, S Basu, S S Yadav, G Narayan, B D Bhatia, A Kumar
OBJECTIVE: Meconium aspiration syndrome (MAS) is a common cause of neonatal morbidity and mortality. Incomplete understanding of the pathogenesis of MAS has hindered the development of specific therapies. We hypothesized that activation of Toll-like receptors (TLRs) might play a role in the pathogenesis of MAS. The present study evaluated the expression of TLR 1, 4, 7, 8 and 9 in neonates with MAS. STUDY DESIGN: The study included 39 neonates with MAS and 17 healthy gestational age-matched neonates as controls...
November 2, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/29061643/a-phase-ib-study-of-immune-biomarker-modulation-with-neoadjuvant-cetuximab-and-tlr8-stimulation-in-head-and-neck-cancer-to-overcome-suppressive-myeloid-signals
#15
Gulidanna Shayan, Benjamin A Kansy, Sandra P Gibson, Raghvendra M Srivastava, James Kyle Bryan, Julie E Bauman, James Ohr, Seungwon Kim, David A Clump, Umamaheswar Duvvuri, Dwight E Heron, Jonas T Johnson, Robert Hershberg, Robert L Ferris
PURPOSE: The response rate of head and neck squamous cell carcinoma (HNSCC) patients to cetuximab therapy is only 15-20%, despite frequent EGFR overexpression. Since immunosuppression is common in HNSCC, we hypothesized that adding a pro-inflammatory TLR8 agonist to cetuximab therapy might result in enhanced T lymphocyte stimulation and anti-EGFR specific priming. EXPERIMENTAL DESIGN: Fourteen patients with previously untreated HNSCC were enrolled in this neoadjuvant trial and treated preoperatively with 3-4 weekly doses of motolimod (2...
October 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29051759/ifn%C3%AE-enhances-cd64-potentiated-phagocytosis-of-treponema-pallidum-opsonized-with-human-syphilitic-serum-by-human-macrophages
#16
Kelly L Hawley, Adriana R Cruz, Sarah J Benjamin, Carson J La Vake, Jorge L Cervantes, Morgan LeDoyt, Lady G Ramirez, Daniza Mandich, Mary Fiel-Gan, Melissa J Caimano, Justin D Radolf, Juan C Salazar
Syphilis is a multi-stage, sexually transmitted disease caused by the spirochete Treponema pallidum (Tp). Considered broadly, syphilis can be conceptualized as a dualistic process in which spirochete-driven inflammation, the cause of clinical manifestations, coexists to varying extents with bacterial persistence. Inflammation is elicited in the tissues, along with the persistence of spirochetes to keep driving a robust immune response while evading host defenses; this duality is best exemplified during the florid, disseminated stage called secondary syphilis (SS)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29042860/toll-like-receptor-8-is-a-major-sensor-of-group-b-streptococcus-but-not-escherichia-coli-in-human-primary-monocytes-and-macrophages
#17
Birgitta Ehrnström, Kai Sandvold Beckwith, Mariia Yurchenko, Siv Helen Moen, June Frengen Kojen, Germana Lentini, Giuseppe Teti, Jan Kristian Damås, Terje Espevik, Jørgen Stenvik
TLR8 is the major endosomal sensor of degraded RNA in human monocytes and macrophages. It has been implicated in the sensing of viruses and more recently also bacteria. We previously identified a TLR8-IFN regulatory factor 5 (IRF5) signaling pathway that mediates IFNβ and interleukin-12 (IL-12) induction by Staphylococcus aureus and is antagonized by TLR2. The relative importance of TLR8 for the sensing of various bacterial species is however still unclear. We here compared the role of TLR8 and IRF5 for the sensing of Group B Streptococcus (GBS), S...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28935693/a-multidimensional-blood-stimulation-assay-reveals-immune-alterations-underlying-systemic-juvenile-idiopathic-arthritis
#18
Alma-Martina Cepika, Romain Banchereau, Elodie Segura, Marina Ohouo, Brandi Cantarel, Kristina Goller, Victoria Cantrell, Emily Ruchaud, Elizabeth Gatewood, Phuong Nguyen, Jinghua Gu, Esperanza Anguiano, Sandra Zurawski, Jeanine M Baisch, Marilynn Punaro, Nicole Baldwin, Gerlinde Obermoser, Karolina Palucka, Jacques Banchereau, Sebastian Amigorena, Virginia Pascual
The etiology of sporadic human chronic inflammatory diseases remains mostly unknown. To fill this gap, we developed a strategy that simultaneously integrates blood leukocyte responses to innate stimuli at the transcriptional, cellular, and secreted protein levels. When applied to systemic juvenile idiopathic arthritis (sJIA), an autoinflammatory disease of unknown etiology, this approach identified gene sets associated with specific cytokine environments and activated leukocyte subsets. During disease remission and off treatment, sJIA patients displayed dysregulated responses to TLR4, TLR8, and TLR7 stimulation...
November 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28923824/snapin-promotes-hiv-1-transmission-from-dendritic-cells-by-dampening-tlr8-signaling
#19
Elham Khatamzas, Madeleine Maria Hipp, Daniel Gaughan, Tica Pichulik, Alasdair Leslie, Ricardo A Fernandes, Daniele Muraro, Sarah Booth, Kieran Zausmer, Mei-Yi Sun, Benedikt Kessler, Sarah Rowland-Jones, Vincenzo Cerundolo, Alison Simmons
HIV-1 traffics through dendritic cells (DCs) en route to establishing a productive infection in T lymphocytes but fails to induce an innate immune response. Within DC endosomes, HIV-1 somehow evades detection by the pattern-recognition receptor (PRR) Toll-like receptor 8 (TLR8). Using a phosphoproteomic approach, we identified a robust and diverse signaling cascade triggered by HIV-1 upon entry into human DCs. A secondary siRNA screen of the identified signaling factors revealed several new mediators of HIV-1 trans-infection of CD4(+) T cells in DCs, including the dynein motor protein Snapin...
October 16, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28919783/toll-like-receptors-7-and-8-expression-correlates-with-the-expression-of-immune-biomarkers-and-positively-predicts-the-clinical-outcome-of-patients-with-melanoma
#20
Moucheng Zhang, Zhilong Yan, Junjiang Wang, Xueqing Yao
BACKGROUND: Toll-like receptors (TLRs) play a critical role in cancer, yet the clinical relevance of TLR7/8 expression in melanoma remains unclear. This study aimed to evaluate the prognostic value of TLR7/8 mRNA levels in melanoma and their correlation with immune biomarkers relevant to disease progression. METHODS: Normalized gene expression and corresponding clinical data of patients with skin cutaneous melanoma were obtained from two public databases: the Cancer Genome Atlas and GSE19234...
2017: OncoTargets and Therapy
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