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https://www.readbyqxmd.com/read/29133347/analysis-of-the-human-mucosal-response-to-cholera-reveals-sustained-activation-of-innate-immune-signaling-pathways
#1
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
#2
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 showed 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28894754/natural-modulators-of-endosomal-toll-like-receptor-mediated-psoriatic-skin-inflammation
#11
REVIEW
Chao-Yang Lai, Yu-Wen Su, Kuo-I Lin, Li-Chung Hsu, Tsung-Hsien Chuang
Psoriasis is a chronic inflammatory autoimmune disease that can be initiated by excessive activation of endosomal toll-like receptors (TLRs), particularly TLR7, TLR8, and TLR9. Therefore, inhibitors of endosomal TLR activation are being investigated for their ability to treat this disease. The currently approved biological drugs adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, and secukizumab are antibodies against effector cytokines that participate in the initiation and development of psoriasis...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28892257/candidate-gene-molecular-markers-as-tools-for-analyzing-genetic-susceptibility-to-morbillivirus-infection-in-stranded-cetaceans
#12
Karla Stejskalova, Zuzana Bayerova, Jan Futas, Kristyna Hrazdilova, Marie Klumplerova, Jan Oppelt, Petra Splichalova, Giovanni Di Guardo, Sandro Mazzariol, Cristina Esmeralda Di Francesco, Gabriella Di Francesco, Giuliana Terracciano, Romulus-Marian Paiu, Teodor Dan Ursache, David Modry, Petr Horin
Morbilliviruses, such as Cetacean morbillivirus (CeMV) or Phocine distemper virus (PDV), represent a growing threat for marine mammals on both hemispheres. Since free-ranging animal populations strongly rely on natural resistance mechanisms, innate immunity related genes and virus cell entry receptor genes may represent key factors involved in susceptibility to CeMV in Cetaceans. Using the next generation sequencing technology, we have sequenced eleven candidate genes in two model species, Stenella coeruleoalba and Phocoena phocoena...
September 11, 2017: HLA
https://www.readbyqxmd.com/read/28887159/integrative-analysis-of-dna-methylation-and-mrna-expression-during-differentiation-of-umbilical-cord-blood-derived-mononuclear-cells-to-endothelial-cells
#13
Yoonjeong Jeong, Yukyung Jun, Jihye Kim, Hyojin Park, Kyu-Sung Choi, Haiying Zhang, Jeong Ae Park, Ja-Young Kwon, Young-Myeong Kim, Sanghyuk Lee, Young-Guen Kwon
Differentiation of umbilical cord blood derived mononuclear cells to endothelial cells is accompanied by massive changes in gene expression. Although methylation and demethylation of DNA likely play crucial roles in regulating gene expression, their interplay during differentiation remains elusive. To address this question, we performed deep sequencing of DNA methylation and mRNA expression to profile global changes in promoter methylation and gene expression during differentiation from mononuclear cells to outgrowing cells...
November 30, 2017: Gene
https://www.readbyqxmd.com/read/28813529/natural-and-artificial-feeding-management-before-weaning-promote-different-rumen-microbial-colonization-but-not-differences-in-gene-expression-levels-at-the-rumen-epithelium-of-newborn-goats
#14
Leticia Abecia, Elisabeth Jiménez, Gonzalo Martínez-Fernandez, A Ignacio Martín-García, Eva Ramos-Morales, Eric Pinloche, Stuart E Denman, C Jamie Newbold, David R Yáñez-Ruiz
The aim of this work was to evaluate the effect of feeding management during the first month of life (natural with the mother, NAT, or artificial with milk replacer, ART) on the rumen microbial colonization and the host innate immune response. Thirty pregnant goats carrying two fetuses were used. At birth one kid was taken immediately away from the doe and fed milk replacer (ART) while the other remained with the mother (NAT). Kids from groups received colostrum during first 2 days of life. Groups of four kids (from ART and NAT experimental groups) were slaughtered at 1, 3, 7, 14, 21 and 28 days of life...
2017: PloS One
https://www.readbyqxmd.com/read/28807280/immunization-with-inactivated-antigens-of-neospora-caninum-induces-toll-like-receptors-3-7-8-and-9-in-maternal-fetal-interface-of-infected-pregnant-heifers
#15
M S Marin, Y P Hecker, S Quintana, S E Pérez, M R Leunda, G J Cantón, E R Cobo, D P Moore, A C Odeón
Neospora caninum is an obligate parasite and a major cause of abortion in cattle. Pregnancy failures appear to be associated with weak innate defences on the maternal-fetal interface during infection with N. caninum. Herein, we studied the gene expression of Toll-like receptors (TLRs) in pregnant heifers immunized with different vaccine formulations against N. caninum before mating and then challenged the heifers with live N. caninum on day 70 of gestation. TLR7 and TLR8 expression was upregulated in the placental caruncle of infected-pregnant heifers previously exposed to live N...
August 30, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28767704/b-abortus-rna-is-the-component-involved-in-the-down-modulation-of-mhc-i-expression-on-human-monocytes-via-tlr8-and-the-egfr-pathway
#16
M Ayelén Milillo, Lis N Velásquez, Aldana Trotta, M Victoria Delpino, Fábio V Marinho, Luciana Balboa, Mónica Vermeulen, Sonia L Espindola, Nahuel Rodriguez-Rodrigues, Gabriela C Fernández, Sergio Costa Oliveira, Guillermo H Giambartolomei, Paula Barrionuevo
Despite eliciting a potent CD8+ T cell response, Brucella abortus is able to persist and establish a chronic infection inside its host. We have previously reported that the infection of human monocytes/macrophages with B. abortus inhibits the IFN-γ-induced MHC-I cell surface expression down-modulating cytotoxic CD8+ T cell responses. MHC-I down-modulation depends on bacterial viability and results from the capacity of B. abortus to retain the MHC-I molecules within the Golgi apparatus. Furthermore, we recently demonstrated that epidermal growth factor receptor (EGFR) pathway is involved in this phenomenon and that this is an early event during infection...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28752959/genetic-variations-in-toll-like-receptors-7-and-8-modulate-natural-hepatitis-c-outcomes-and-liver-disease-progression
#17
Fatima-Zohra Fakhir, Mustapha Lkhider, Wafaa Badre, Rhimou Alaoui, Eliane F Meurs, Pascal Pineau, Sayeh Ezzikouri, Soumaya Benjelloun
BACKGROUND & AIMS: The natural outcomes of hepatitis C virus (HCV) as well as the progression of the liver disease are highly variable and depend primarily on an efficient immune response. As Toll-like receptors 7 (TLR7) and 8 (TLR8) are important effectors of the innate immunity, the present study aims to evaluate the association between TLR7 and TLR8 polymorphisms and the HCV infection outcomes in Moroccan subjects. METHODS: In this case-control study, 643 subjects including 293 mild chronic hepatitis patients, 119 with advanced liver disease (AdLD), 93 with HCV spontaneous clearance and 138 healthy controls were genotyped using TaqMan SNPs assays...
July 28, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28744288/naltrexone-inhibits-il-6-and-tnf%C3%AE-production-in-human-immune-cell-subsets-following-stimulation-with-ligands-for-intracellular-toll-like-receptors
#18
Rachel Cant, Angus G Dalgleish, Rachel L Allen
The opioid antagonist naltrexone hydrochloride has been suggested to be a potential therapy at low dosage for multiple inflammatory conditions and cancers. Little is known about the immune-modulating effects of naltrexone, but an effect on the activity of toll-like receptor 4 (TLR4) has been reported. We analyzed the effects of naltrexone hydrochloride on IL-6 secretion by peripheral blood mononuclear cells (PBMC) in vitro following stimulation with ligands for TLR4 and for the intracellular receptors TLR7, TLR8, and TLR9...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28698123/identification-molecular-evolution-of-toll-like-receptors-in-a-tibetan-schizothoracine-fish-gymnocypris-eckloni-and-their-expression-profiles-in-response-to-acute-hypoxia
#19
Delin Qi, Mingzhe Xia, Yan Chao, Yongli Zhao, Rongrong Wu
Hypoxia plays an important role in regulating a variety of physiological responses as well as in pathological situations, but to date the roles of Toll-like receptors (TLRs) in fish in response to hypoxia are still poorly understood. Here, we sequenced the transcriptome of G. eckloni and identified the members of TLR family by scanning transcriptome, and then investigated the expression profiles of a complete set of TLRs in G. eckloni in response to acute hypoxia (4 h at DO = 0.3 ± 0.1 mg/L). The de novo-assembled transcriptome consisted of a total of 162,235 transcripts, further clustered into 110,231 unigenes...
July 8, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28671847/identification-and-optimization-of-pyrrolo-3-2-d-pyrimidine-toll-like-receptor-7-tlr7-selective-agonists-for-the-treatment-of-hepatitis-b
#20
David C McGowan, Florence Herschke, Frederik Pauwels, Bart Stoops, Ilham Smyej, Stefaan Last, Serge Pieters, Werner Embrechts, Mourad Daoubi Khamlichi, Tine Thoné, Bertrand Van Schoubroeck, Wendy Mostmans, Debbie Wuyts, Dorien Verstappen, Annick Scholliers, Dorien De Pooter, Deborah Dhuyvetter, Herman Borghys, Marianne Tuefferd, Eric Arnoult, Jin Hong, Gregory Fanning, Jacques Bollekens, Vijay Urmaliya, Ard Teisman, Helen Horton, Tim H M Jonckers, Pierre Raboisson
Pyrrolo[3,2-d]pyrimidines were identified as a new series of potent and selective TLR7 agonists. Compounds were optimized for their activity and selectivity over TLR8. This presents an advantage over recently described scaffolds that have residual TLR8 activity, which may be detrimental to the tolerability of the candidate drug. Oral administration of the lead compound 54 effectively induced a transient interferon stimulated gene (ISG) response in mice and cynomolgus monkeys. We aimed for a high first pass effect, limiting cytokine induction systemically, and demonstrated the potential for the immunotherapy of viral hepatitis...
July 27, 2017: Journal of Medicinal Chemistry
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