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TLR agonist

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https://www.readbyqxmd.com/read/28432455/dual-activation-of-toll-like-receptors-7-and-9-impairs-the-efficacy-of-antitumor-vaccines-in-murine-models-of-metastatic-breast-cancer
#1
Mariela A Moreno Ayala, María Florencia Gottardo, María Soledad Gori, Alejandro Javier Nicola Candia, Carla Caruso, Andrea De Laurentiis, Mercedes Imsen, Slobodanka Klein, Elisa Bal de Kier Joffé, Gabriela Salamone, Maria G Castro, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. METHODS: DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28432147/cutting-edge-a-dual-tlr2-and-tlr7-ligand-induces-highly-potent-humoral-and-cell-mediated-immune-responses
#2
Alice Gutjahr, Laura Papagno, Francesco Nicoli, Alain Lamoureux, Fabienne Vernejoul, Thierry Lioux, Emma Gostick, David A Price, Gérard Tiraby, Eric Perouzel, Victor Appay, Bernard Verrier, Stéphane Paul
TLR agonists are currently being developed and tested as adjuvants in various formulations to optimize the immunogenicity and efficacy of vaccines. The aim of this study was to evaluate the immunostimulatory properties of a novel compound incorporating covalently linked moieties designed to stimulate both TLR2 and TLR7. This dual TLR2/TLR7 agonist induced the maturation of dendritic cells and primed substantial populations of cytolytic and highly polyfunctional effector CD8(+) T cells in vitro, and safely potentiated the immunogenic properties of a nanoparticulate Ag in vivo, eliciting humoral responses with a balanced TH1/TH2 profile in mice...
April 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28429728/a-formulated-tlr7-8-agonist-is-a-flexible-highly-potent-and-effective-adjuvant-for-pandemic-influenza-vaccines
#3
Neal Van Hoeven, Christopher B Fox, Brian Granger, Tara Evers, Sharvari W Joshi, Ghislain I Nana, Sarah C Evans, Susan Lin, Hong Liang, Li Liang, Rie Nakajima, Philip L Felgner, Richard A Bowen, Nicole Marlenee, Airn Hartwig, Susan L Baldwin, Rhea N Coler, Mark Tomai, James Elvecrog, Steven G Reed, Darrick Carter
Since 1997, highly pathogenic avian influenza viruses of the H5N1 subtype have been transmitted from avian hosts to humans. The severity of H5N1 infection in humans, as well as the sporadic nature of H5N1 outbreaks, both geographically and temporally, make generation of an effective vaccine a global public health priority. An effective H5N1 vaccine must ultimately provide protection against viruses from diverse clades. Toll-like receptor (TLR) agonist adjuvant formulations have a demonstrated ability to broaden H5N1 vaccine responses in pre-clinical models...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28410380/interleukin-10-and-prostaglandin-e2-have-complementary-but-distinct-suppressive-effects-on-toll-like-receptor-mediated-dendritic-cell-activation-in-ovarian-carcinoma
#4
Eva Brencicova, Ann L Jagger, Hayley G Evans, Mirella Georgouli, Alex Laios, Steve Attard Montalto, Gautam Mehra, Jo Spencer, Ahmed A Ahmed, Shanti Raju-Kankipati, Leonie S Taams, Sandra S Diebold
Dendritic cells (DC) have the potential to instigate a tumour-specific immune response, but their ability to prime naïve lymphocytes depends on their activation status. Thus, for tumour immunotherapy to be effective, the provision of appropriate DC activation stimuli such as Toll-like receptor (TLR) agonists is crucial in order to overcome immunosuppression associated with the tumour microenvironment. To address this, we investigated how ovarian carcinoma (OC)-associated ascites impedes activation of DC by TLR agonists...
2017: PloS One
https://www.readbyqxmd.com/read/28407632/hypothermic-neuronal-rescue-from-infection-sensitised-hypoxic-ischaemic-brain-injury-is-pathogen-dependent
#5
Mari Falck, Damjan Osredkar, Elke Maes, Torun Flatebø, Thomas Ragnar Wood, Hemmen Sabir, Marianne Thoresen
Perinatal infection increases the vulnerability of the neonatal brain to hypoxic-ischaemic (HI) injury. Hypothermia treatment (HT) does not provide neuroprotection after pre-insult inflammatory sensitisation by lipopolysaccharide (LPS), a gram-negative bacterial wall constituent. However, early-onset sepsis in term babies is caused by gram-positive species in more than 90% of cases, and neuro-inflammatory responses triggered through the gram-negative route (Toll-like receptor 4, TLR-4) are different from those induced through the gram-positive route via TLR-2...
April 14, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28405594/screening-for-novel-endogenous-inflammatory-stimuli-using-the-secreted-embryonic-alkaline-phosphatase-nf-%C3%AE%C2%BAb-reporter-assay
#6
Lorena Zuliani-Alvarez, Anna M Piccinini, Kim S Midwood
An immune response can be activated by pathogenic stimuli, as well as endogenous danger signals, triggering the activation of pattern recognition receptors and initiating signalling cascades that lead to inflammation. This method uses THP1-Blue™ cells, a human monocytic cell line which contains an embryonic alkaline phosphatase reporter gene allowing the detection of NF-κB-induced transcriptional activation. We validated this protocol by assessing NF-κB activation after stimulation of toll-like receptor 4 (TLR4) by two different agonists: lipopolysaccharide (LPS), derived from the cell wall of Gram negative bacteria, and tenascin-C, an extracellular matrix protein whose expression is induced upon tissue injury...
April 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28402258/cd200fc-reduces-lps-induced-il-1%C3%AE-activation-in-human-cervical-cancer-cells-by-modulating-tlr4-nf-%C3%AE%C2%BAb-and-nlrp3-inflammasome-pathway
#7
Aiqin He, Jia Shao, Yu Zhang, Hong Lu, Zhijun Wu, Yunzhao Xu
Chronic inflammation plays an important role in tumorigenesis of cervical cancer. CD200Fc, a CD200R1 agonist, has been found to have anti-inflammatory effects in autoimmune diseases and neuro-degeneration. However, the anti-inflammatory effect of CD200Fc on cervical cancer has not yet to be completely understood. This study investigated the anti-inflammatory effects and mechanisms of CD200Fc in LPS-induced human SiHa cells and Caski cells. SiHa cells and Caski cells were stimulated with 40 μg/ml LPS under different concentrations of CD200Fc for 90 min or 12 hours...
March 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398147/salmeterol-a-long-acting-%C3%AE-2-aderenergic-receptor-agonist-inhibits-macrophage-activation-by-lipopolysaccharide-from-porphyromonas-gingivalis
#8
Monika Sharma, Lindsay Patterson, Elisha Chapman, Patrick M Flood
BACKGROUND: Salmeterol is a long-acting beta-2 adrenergic receptor (β2AR) agonist that is used to treat chronic obstructive pulmonary disease (COPD). Previously we had shown that pre-incubation of primary microglial enriched cells with Salmeterol could inhibit the inflammatory response induced by E. Coli LPS, a TLR-4 (toll-like receptor-4) agonist. In this study, we sought to determine if Salmeterol had a similar inhibitory effect on the inflammatory response of the murine macrophage cell line RAW264...
March 3, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28388966/vaccination-with-poly-ic-lc-and-peptide-pulsed-autologous-dendritic-cells-in-patients-with-pancreatic-cancer
#9
Shikhar Mehrotra, Carolyn D Britten, Steve Chin, Elizabeth Garrett-Mayer, Colleen A Cloud, Mingli Li, Gina Scurti, Mohamed L Salem, Michelle H Nelson, Melanie B Thomas, Chrystal M Paulos, Andres M Salazar, Michael I Nishimura, Mark P Rubinstein, Zihai Li, David J Cole
BACKGROUND: Dendritic cells (DCs) enhance the quality of anti-tumor immune response in patients with cancer. Thus, we posit that DC-based immunotherapy, in conjunction with toll-like receptor (TLR)-3 agonist poly-ICLC, is a promising approach for harnessing immunity against metastatic or locally advanced unresectable pancreatic cancer (PC). METHODS: We generated autologous DCs from the peripheral blood of HLA-A2(+) patients with PC. DCs were pulsed with three distinct A2-restricted peptides: 1) human telomerase reverse transcriptase (hTERT, TERT572Y), 2) carcinoembryonic antigen (CEA; Cap1-6D), and 3) survivin (SRV...
April 7, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28383274/past-current-and-future-developments-of-therapeutic-agents-for-treatment-of-chronic-hepatitis-b-virus-infection
#10
Yameng Pei, Chunting Wang, S Frank Yan, Gang Liu
For decades, treatment of hepatitis B virus (HBV) infection has been relying on interferon (IFN)-based therapies and nucleoside/nucleotide analogues (NAs) that selectively target the viral polymerase reverse transcriptase (RT) domain and thereby disrupt HBV viral DNA synthesis. We have summarized here the key steps in the HBV viral life cycle, which could potentially be targeted by novel anti-HBV therapeutics. A wide range of next-generation direct antiviral agents (DAAs) with distinct mechanisms of actions are discussed, including entry inhibitors, transcription inhibitors, nucleoside/nucleotide analogues, inhibitors of viral ribonuclease H (RNase H), modulators of viral capsid assembly, inhibitors of HBV surface antigen (HBsAg) secretion, RNA interference (RNAi) gene silencers, antisense oligonucleotides (ASOs), and natural products...
April 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28382943/badger-macrophages-fail-to-produce-nitric-oxide-a-key-anti-mycobacterial-effector-molecule
#11
Kirstin Bilham, Amy C Boyd, Stephen G Preston, Christina D Buesching, Chris Newman, David W Macdonald, Adrian L Smith
The European badger is recognised as a wildlife reservoir for bovine tuberculosis (bTB); the control of which is complex, costly and controversial. Despite the importance of badgers in bTB and the well-documented role for macrophages as anti-mycobacterial effector cells, badger macrophage (bdMφ) responses remain uncharacterised. Here, we demonstrate that bdMφ fail to produce nitric oxide (NO) or upregulate inducible nitric oxide synthase (iNOS) mRNA following Toll-like receptor (TLR) agonist treatment. BdMφ also failed to make NO after stimulation with recombinant badger interferon gamma (bdIFNγ) or a combination of bdIFNγ and lipopolysaccharide...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28373665/polyfunctional-natural-killer-cells-with-a-low-activation-profile-in-response-to-toll-like-receptor-3-activation-in-hiv-1-exposed-seronegative-subjects
#12
Josenilson F Lima, Luanda M S Oliveira, Nátalli Z Pereira, Alberto J S Duarte, Maria N Sato
Natural killer (NK) cells are the main mediator of the cytotoxic response in innate immunity and may be involved in resistance to HIV-1 infection in exposed seronegative (ESN) individuals. Toll-like receptor (TLR) signalling is crucial for NK cell activation. Here, we investigated the polyfunctional NK cell response to TLR3 activation in serodiscordant couples. ESN subjects showed increased IFN-γ and CD107a expression in both NK subsets, CD56(bright) and CD56(dim) cells, in response to stimulation with a TLR3 agonist, while expression was impaired in the HIV-1-infected partners...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28369600/involvement-of-reactive-oxygen-species-in-ionizing-radiation-induced-upregulation-of-cell-surface-toll-like-receptor-2-and-4-expression-in-human-monocytic-cells
#13
Hironori Yoshino, Ikuo Kashiwakura
Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen-associated molecular patterns and are indispensable for antibacterial and antiviral immunity. Our previous report showed that ionizing radiation increases the cell surface expressions of TLR2 and TLR4 and enhances their responses to agonists in human monocytic THP1 cells. The present study investigated how ionizing radiation increases the cell surface expressions of TLR2 and TLR4 in THP1 cells. The THP1 cells treated or not treated with pharmaceutical agents such as cycloheximide and N-acetyl-L-cysteine (NAC) were exposed to X-ray irradiation, following which the expressions of TLRs and mitogen-activated protein kinase were analyzed...
March 22, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28362018/il-37-suppresses-myd88-mediated-inflammatory-responses-in-human-aortic-valve-interstitial-cells
#14
Qiong Zhan, Qingchun Zeng, Rui Song, Yufeng Zhai, Dingli Xu, David A Fullerton, Charles A Dinarello, Xianzhong Meng
BACKGROUND: Calcific aortic valve disease (CAVD) is common among the elderly, and aortic valve interstitial cells (AVICs) exhibit unique inflammatory and osteogenic responses to pro-inflammatory stimulation which play an important role in valvular fibrosis and calcification. Thus, suppression of AVIC pro-inflammatory response may have therapeutic utility for prevention of CAVD progression. Interleukin (IL)-37, an anti-inflammatory cytokine, reduces tissue inflammation. OBJECTIVE: This study was to test the hypothesis that IL-37 suppresses human AVIC inflammatory responses to Toll-like receptor (TLR) agonists...
March 27, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28352660/tlr7-8-adjuvant-overcomes-newborn-hyporesponsiveness-to-pneumococcal-conjugate-vaccine-at-birth
#15
David J Dowling, Simon D van Haren, Annette Scheid, Ilana Bergelson, Dhohyung Kim, Christy J Mancuso, Willemina Foppen, Al Ozonoff, Lynn Fresh, Terese B Theriot, Andrew A Lackner, Raina N Fichorova, Dmitri Smirnov, John P Vasilakos, Joe M Beaurline, Mark A Tomai, Cecily C Midkiff, Xavier Alvarez, James L Blanchard, Margaret H Gilbert, Pyone Pyone Aye, Ofer Levy
Infection is the most common cause of mortality in early life, and immunization is the most promising biomedical intervention to reduce this burden. However, newborns fail to respond optimally to most vaccines. Adjuvantation is a key approach to enhancing vaccine immunogenicity, but responses of human newborn leukocytes to most candidate adjuvants, including most TLR agonists, are functionally distinct. Herein, we demonstrate that 3M-052 is a locally acting lipidated imidazoquinoline TLR7/8 agonist adjuvant in mice, which, when properly formulated, can induce robust Th1 cytokine production by human newborn leukocytes in vitro, both alone and in synergy with the alum-adjuvanted pneumococcal conjugate vaccine 13 (PCV13)...
March 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28350104/induction-of-galectin-1-by-tlr-dependent-pi3k-activation-enhances-epithelial-mesenchymal-transition-of-metastatic-ovarian-cancer-cells
#16
Ga Bin Park, Yoon Hee Chung, Daejin Kim
The expression of different toll-like receptors (TLRs) on tumor cells has been associated with disease aggressiveness, treatment resistance, and poor prognosis. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is considered critical for cancer cell survival and proliferation. Thus, we investigated the effect of TLR-stimulated PI3K activation on the epithelial-to-mesenchymal transition (EMT) of primary (Caov-3) and metastatic (SK‑OV‑3) epithelial ovarian cancer cell lines in this study. TLR engagement with various ligands promoted the expression of class IA PI3K (p110α, p110β, and p110δ) and increased the expression of mesenchymal markers (N-cadherin, Slug, Vimentin, Snail, α-SMA, and TCF) in SK‑OV‑3 cells...
March 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28348558/microbiota-immune-subversion-and-chronic-inflammation
#17
REVIEW
Carolyn D Kramer, Caroline Attardo Genco
Several host-adapted pathogens and commensals have evolved mechanisms to evade the host innate immune system inducing a state of low-grade inflammation. Epidemiological studies have also documented the association of a subset of these microorganisms with chronic inflammatory disorders. In this review, we summarize recent studies demonstrating the role of the microbiota in chronic inflammatory diseases and discuss how specific microorganisms subvert or inhibit protective signaling normally induced by toll-like receptors (TLRs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28343701/toll-like-receptor-8-agonist-nanoparticles-mimic-immunomodulating-effects-of-the-live-bcg-vaccine-and-enhance-neonatal-innate-and-adaptive-immune-responses
#18
David J Dowling, Evan A Scott, Annette Scheid, Ilana Bergelson, Sweta Joshi, Carlo Pietrasanta, Spencer Brightman, Guzman Sanchez-Schmitz, Simon D Van Haren, Jana Ninković, Dina Kats, Cristiana Guiducci, Alexandre de Titta, Daniel K Bonner, Sachiko Hirosue, Melody A Swartz, Jeffrey A Hubbell, Ofer Levy
BACKGROUND: Newborns display distinct immune responses, leaving them vulnerable to infections and impairing immunization. Targeting newborn dendritic cells (DCs), which integrate vaccine signals into adaptive immune responses, might enable development of age-specific vaccine formulations to overcome suboptimal immunization. OBJECTIVE: Small-molecule imidazoquinoline Toll-like receptor (TLR) 8 agonists robustly activate newborn DCs but can result in reactogenicity when delivered in soluble form...
March 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28342266/increased-number-of-mast-cells-in-the-dermis-in-actinic-keratosis-lesions-effectively-treated-with-imiquimod
#19
Satomi Oyama, Yoko Funasaka, Shin-Ichi Tsuchiya, Seiji Kawana, Hidehisa Saeki
Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll-like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non-melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the course of treatment of AK. In addition, mast cells are now considered to contribute to both the innate and adaptive immune systems in topical imiquimod therapy. We assessed the effect of imiquimod treatment by dermatoscopic and immunohistochemical findings in 14 patients with a total of 21 AK lesions...
March 24, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28329288/tlr-agonists-can-they-exact-a-toll-on-hiv-persistence
#20
Joshua C Cyktor, John W Mellors
No abstract text is available yet for this article.
March 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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