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https://www.readbyqxmd.com/read/29656235/effective-cancer-immunotherapy-in-mice-by-polyic-imiquimod-complexes-and-engineered-magnetic-nanoparticles
#1
Ana Isabel Bocanegra Gondan, Ane Ruiz-de-Angulo, Aintzane Zabaleta, Nina Gómez Blanco, Beatriz Macarena Cobaleda-Siles, María Jesús García-Granda, Daniel Padro, Jordi Llop, Blanca Arnaiz, María Gato, David Escors, Juan C Mareque-Rivas
Encouraging results are emerging from systems that exploit Toll like receptor (TLR) signaling, nanotechnology, checkpoint inhibition and molecular imaging for cancer immunotherapy. A major remaining challenge is developing effective, durable and tumour-specific immune responses without systemic toxicity. Here, we report a simple and versatile system based on synergistic activation of immune responses and direct cancer cell killing by combined TLR ligation using polyIC as TLR3 and imiquimod (R837) as TLR7 agonist, in combination with the model antigen ovalbumin (OVA) and phospholipid micelles loaded with zinc-doped iron oxide magnetic nanoparticles (MNPs)...
April 3, 2018: Biomaterials
https://www.readbyqxmd.com/read/29610858/high-mobility-group-box-1-in-dry-eye-inflammation
#2
Carolina Lema, Rose Y Reins, Rachel L Redfern
Purpose: To determine high-mobility group box 1 (HMGB1) expression during experimental dry eye (EDE) and dry eye-like culture conditions and elucidate its role in corneal dry eye-related inflammation. Methods: EDE was induced in 8- to 12-week-old C57BL/6 mice. Corneal tissue sections and lysates from EDE and untreated mice were evaluated for HMGB1 expression by immunostaining and quantitative real-time PCR (qPCR). For in vitro studies, human corneal epithelial cells (HCEC) were treated with hyperosmolar media, toll-like receptor (TLR) agonists, or proinflammatory cytokines to determine HMGB1 expression...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29609129/nebulized-lidocaine-ameliorates-allergic-airway-inflammation-via-downregulation-of-tlr2
#3
Lixia Wang, Muzi Wang, Shuai Li, Huimei Wu, Qiying Shen, Shihai Zhang, Lei Fang, Rongyu Liu
Nebulized lidocaine has been suggested to be beneficial in asthma therapy, but the underlying mechanisms are little known. We aimed to investigate whether Toll-like receptor (TLR) 2 was involved in the protective effect of lidocaine on allergic airway inflammation. Female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA). Meanwhile, some of the mice were treated with TLR2 agonist (Pam3CSK4, 100 μg) intraperitoneally in combination with OVA on day 0. Just after allergen provocation, mice were treated with inhaled lidocaine or vehicle for 30 min...
March 30, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29608601/sting-agonists-enable-antiviral-cross-talk-between-human-cells-and-confer-protection-against-genital-herpes-in-mice
#4
Morten K Skouboe, Alice Knudsen, Line S Reinert, Cedric Boularan, Thierry Lioux, Eric Perouzel, Martin K Thomsen, Søren R Paludan
In recent years, there has been an increasing interest in immunomodulatory therapy as a means to treat various conditions, including infectious diseases. For instance, Toll-like receptor (TLR) agonists have been evaluated for treatment of genital herpes. However, although the TLR7 agonist imiquimod was shown to have antiviral activity in individual patients, no significant effects were observed in clinical trials, and the compound also exhibited significant side effects, including local inflammation. Cytosolic DNA is detected by the enzyme cyclic GMP-AMP (2'3'-cGAMP) synthase (cGAS) to stimulate antiviral pathways, mainly through induction of type I interferon (IFN)s...
April 2, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29603875/toll-like-receptor-2-and-3-enhance-melanogenesis-and-melanosome-transport-in-human-melanocytes
#5
AutSaaya Koike, Kenshi Yamasaki, Takeshi Yamauchi, Mai Inoue, Ryoko Shimada-Ohmori, Kenichiro Tsuchiyama, Setsuya Aiba
Because little is known about how the innate immune response influences skin pigmentation, we examined whether Toll-like receptor (TLR) agonists participate in melanogenesis and melanosome transportation. We observed that TLR2/2 agonist HKLM and TLR3 agonist Poly(I:C) increased the amount of extracellular melanin from primary human epidermal melanocytes. HKLM, but not Poly(I:C), increased the melanogenic genes such as tyrosinase and dopachrome tautomerase. Poly(I:C) increased the expression of Rab27A, a molecule that facilitates melanosome transport to perimembranous actin filament...
March 30, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29599452/direct-antiviral-properties-of-tlr-ligands-against-hbv-replication-in-immune-competent-hepatocytes
#6
Julie Lucifora, Marc Bonnin, Ludovic Aillot, Floriane Fusil, Sarah Maadadi, Laura Dimier, Maud Michelet, Océane Floriot, Anaïs Ollivier, Michel Rivoire, Malika Ait-Goughoulte, Stéphane Daffis, Simon P Fletcher, Anna Salvetti, François-Loïc Cosset, Fabien Zoulim, David Durantel
Current therapies for chronic hepatitis B virus (HBV) infections are effective at decreasing the viral load in serum, but do not lead to viral eradication. Recent studies highlighted the therapeutic or "adjuvant" potential of immune-modulators. Our aim was to explore the direct anti-HBV effect of Toll-Like-Receptors (TLR) agonists in hepatocytes. HBV-infected primary human hepatocytes (PHH) or differentiated HepaRG cells (dHepaRG) were treated with various TLR agonists. Amongst all TLR ligands tested, Pam3CSK4 (TLR1/2-ligand) and poly(I:C)-(HMW) (TLR3/MDA5-ligand) were the best at reducing all HBV parameters...
March 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29588627/zymosan-attenuates-melanoma-growth-progression-increases-splenocyte-proliferation-and-induces-tlr-2-4-and-tnf-%C3%AE-expression-in-mice
#7
Mehdi Taghavi, Esmaeil Mortaz, Alireza Khosravi, Ghasem Vahedi, Gert Folkerts, Mohammad Varahram, Mehdi Kazempour-Dizaji, Johan Garssen, Ian M Adcock
Background: Melanoma is one of the most common types of skin malignancies. Since current therapies are suboptimal, considerable interest has focused on novel natural-based treatments. Toll-like receptors (TLRs) play an important role in evoking innate immunity against cancer cells. Zymosan, a known TLR-2 agonist, is a glucan derived from yeast cell walls with promising immunomodulatory effects. The aim of this study was to evaluate whether Saccharomyces cerevisiae -derived zymosan-modulated skin melanoma progression by regulation of TLR-2 and TLR-4 expression in peritoneal macrophages and serum TNF-α level...
2018: Journal of Inflammation
https://www.readbyqxmd.com/read/29582430/human-periodontal-ligament-cells-exhibit-no-endotoxin-tolerance-upon-stimulation-with-porphyromonas-gingivalis-lipopolysaccharide
#8
A Blufstein, C Behm, P Q Nguyen, X Rausch-Fan, O Andrukhov
BACKGROUND/OBJECTIVES: Endotoxin tolerance is characterized by a state of hyporesponsiveness after confrontation with endotoxins such as lipopolysaccharides (LPS) at low concentrations. The aim of this study was to investigate, whether pretreatment with Porphyromonas gingivalis leads to endotoxin tolerance induction and possible alterations in toll-like receptor (TLR) 2- and 4-induced response in human periodontal ligament cells (hPDLCs). MATERIAL AND METHODS: Primary hPDLCs were pretreated with P...
March 26, 2018: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29569859/toll-like-receptor-7-8-activation-exacerbates-murine-experimental-autoimmune-myositis
#9
Clara Sciorati, Antonella Monno, Maria Giulia Doglio, Elena Rigamonti, Dana P Ascherman, Angelo A Manfredi, Patrizia Rovere-Querini
OBJECTIVE: TLR-7/8 and Interferon (IFN)-induced genes are expressed in patients with inflammatory idiopathic myositis. Here we investigated whether their activation influences the natural history of the disease. METHODS: Experimental autoimmune myositis (EAM) was induced by injection of the amino-terminal portion of the murine Histydil t-RNA synthetase (HisRS). Disease was compared in the presence or the absence of the TLR-7/8 agonist R848 in wild-type mice and in mice that fail to express the IFNαβ receptor (IFNαβR null)...
March 23, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29567135/class-b-cpg-odn2006-is-highly-associated-with-igm-and-antimicrobial-peptide-gene-expression-through-tlr9-pathway-in-yellowtail-seriola-lalandi
#10
Carlos Angulo, Erika Alamillo, Ikuo Hirono, Hidehiro Kondo, Walissara Jirapongpairoj, Juan Carlos Perez-Urbiola, Martha Reyes-Becerril
The purpose of this study was to characterize the TLR9 gene from yellowtail (Seriola lalandi) and evaluate its functional activity using the class B Cytosine-phosphate-guanine-oligodeoxynucleotide2006 (CpG-ODN2006) in an in vivo experiment after one-week immunostimulation. The gene expressions of TLR9, Immunoglobulin M (IgM), antimicrobial peptides and cytokines were evaluated by real time PCR, and humoral immune parameters were analyzed in serum. The TLR9 nucleotide sequence from yellowtail was obtained using the whole-genome shotgun sequencing method and bioinformatics tools...
March 19, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29556002/recognition-of-microbial-viability-via-tlr8-drives-t-fh-cell-differentiation-and-vaccine-responses
#11
Matteo Ugolini, Jenny Gerhard, Sanne Burkert, Kristoffer Jarlov Jensen, Philipp Georg, Friederike Ebner, Sarah M Volkers, Shruthi Thada, Kristina Dietert, Laura Bauer, Alexander Schäfer, Elisa T Helbig, Bastian Opitz, Florian Kurth, Saubashya Sur, Nickel Dittrich, Sumanlatha Gaddam, Melanie L Conrad, Christine S Benn, Ulrike Blohm, Achim D Gruber, Andreas Hutloff, Susanne Hartmann, Mark V Boekschoten, Michael Müller, Gregers Jungersen, Ralf R Schumann, Norbert Suttorp, Leif E Sander
Live attenuated vaccines are generally highly efficacious and often superior to inactivated vaccines, yet the underlying mechanisms of this remain largely unclear. Here we identify recognition of microbial viability as a potent stimulus for follicular helper T cell (TFH cell) differentiation and vaccine responses. Antigen-presenting cells (APCs) distinguished viable bacteria from dead bacteria through Toll-like receptor 8 (TLR8)-dependent detection of bacterial RNA. In contrast to dead bacteria and other TLR ligands, live bacteria, bacterial RNA and synthetic TLR8 agonists induced a specific cytokine profile in human and porcine APCs, thereby promoting TFH cell differentiation...
March 19, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29552145/novel-tlr7-agonist-stimulates-activity-of-cik-nk-immunological-effector-cells-to-enhance-antitumor-cytotoxicity
#12
Dong Gao, Yongguang Cai, Yanyuan Chen, Wang Li, Chih-Chang Wei, Xiaoling Luo, Yuhuan Wang
Toll-like receptor (TLR) 7/8 agonists have been applied in combination with chemo-, radio- or immunotherapy for lymphoma, and used as topical drugs for the treatment of viral skin lesions and skin tumors. In the present study, the role of an adenine analog, 9-(4-carboxyphenyl)-8-hydroxy-2-(2-methoxyethoxy)-adenine [termed Gao Dong (GD)], a novel TLR7 agonist, in the activation of cytokine-induced killer/natural killer (CIK/NK) cells was determined. The results of the present study indicated that GD was able to activate CIK/NK cells...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29544515/next-generation-of-immune-checkpoint-therapy-in-cancer-new-developments-and-challenges
#13
REVIEW
Julian A Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E Soyano, Keith L Knutson, Saranya Chumsri, Yanyan Lou
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways...
March 15, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29535517/the-effects-of-repeated-toll-like-receptors-2-and-4-stimulation-in-copd-alveolar-macrophages
#14
Simon R Lea, Sophie L Reynolds, Manminder Kaur, Karen D Simpson, Simon R Hall, Edith M Hessel, Dave Singh
Background: COPD is a progressive inflammatory airway disease characterized by increased numbers of alveolar macrophages in the lungs. Bacterial colonization of the lungs is a common feature in COPD and can promote inflammation through continual and repeated Toll-like receptor (TLR) stimulation. We have studied the response of COPD alveolar macrophages to repetitive stimulation with TLR2 and TLR4 ligands. We investigated the effect of sequential stimulation with different ligands to determine whether this results in tolerance or amplification of the immune response...
2018: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29530841/tlr7-agonists-display-potent-antiviral-effects-against-norovirus-infection-via-innate-stimulation
#15
Daniel Enosi Tuipulotu, Natalie E Netzler, Jennifer H Lun, Jason M Mackenzie, Peter A White
Norovirus infections are a significant health and economic burden globally, accounting for hundreds of millions of cases of acute gastroenteritis every year. In the absence of an approved norovirus vaccine, there is an urgent need to develop antivirals to treat chronic infections, and provide prophylactic therapy to limit viral spread during epidemics and pandemics. Toll-like receptor (TLR) agonists have been explored widely for their antiviral potential and several are progressing through clinical trials for the treatment of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and as adjuvants for norovirus virus-like particle (VLP) vaccines...
March 12, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29528268/platelet-toll-like-receptor-expression-and-activation-induced-by-lipopolysaccharide-and-sepsis
#16
Theodora A M Claushuis, Annelou I P Van Der Veen, Janneke Horn, Marcus J Schultz, Riekelt H Houtkooper, Cornelis Van 't Veer, Tom Van Der Poll
Platelets and Toll-like receptor (TLR) signalling play a role in the immune response during sepsis. Although preclinical knowledge about the role of platelet TLR signalling is increasing, data during human sepsis are less abundant. Moreover, controversy remains about the effect of the TLR4 agonist lipopolysaccharide (LPS) on platelet activation. We therefore assessed platelet TLR expression during human and murine sepsis. Moreover, we investigated the effect of TLR4 signalling on platelet activation and TLR expression...
March 12, 2018: Platelets
https://www.readbyqxmd.com/read/29526974/adjuvant-immunotherapy-for-cancer-both-dendritic-cell-priming-and-check-point-inhibitor-blockade-are-required-for-immunotherapy
#17
Tsukasa Seya, Yohei Takeda, Ken Takashima, Sumito Yoshida, Masahiro Azuma, Misako Matsumoto
The immune system eliminates advanced cancer when treated with programmed cell death protein-1 (PD-1) or its ligand (PD-L1) blockade, but PD-1 therapy is effective in only ∼20% of patients with solid cancer. The PD-1 antibody mainly acts on the effector phase of cytotoxic T lymphocytes (CTLs) in tumors but induces no activation of the priming phase of antigen-presenting dendritic cells (DCs). It is reasonable that both DC-priming and PD-1/L1 blocking are mandatory for efficient CTL-mediated tumor cytolysis...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/29518743/andrographolide-suppresses-trif-dependent-signaling-of-toll-like-receptors-by-targeting-tbk1
#18
Ah-Yeon Kim, Hyun-Jin Shim, Hyeon-Myeong Shin, Yoo Jung Lee, Hyeonjeong Nam, Su Yeon Kim, Hyung-Sun Youn
Toll-like receptors (TLRs) play a crucial role in danger recognition and induction of innate immune response against bacterial and viral infections. The TLR adaptor molecule, toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF), facilitates TLR3 and TLR4 signaling, leading to the activation of the transcription factor, NF-κB and interferon regulatory factor 3 (IRF3). Andrographolide, the active component of Andrographis paniculata, exerts anti-inflammatory effects; however, the principal molecular mechanisms remain unclear...
April 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29515589/improved-immune-responses-in-young-and-aged-mice-with-adjuvanted-vaccines-against-h1n1-influenza-infection
#19
Susan L Baldwin, Fan-Chi Hsu, Neal Van Hoeven, Emily Gage, Brian Granger, Jeffrey A Guderian, Sasha E Larsen, Erica C Lorenzo, Laura Haynes, Steven G Reed, Rhea N Coler
Elderly people are at high risk for influenza-related morbidity and mortality due to progressive immunosenescence. While toll-like receptor (TLR) agonist containing adjuvants, and other adjuvants, have been shown to enhance influenza vaccine-induced protective responses, the mechanisms underlying how these adjuvanted vaccines could benefit the elderly remain elusive. Here, we show that a split H1N1 influenza vaccine (sH1N1) combined with a TLR4 agonist, glucopyranosyl lipid adjuvant formulated in a stable oil-in-water emulsion (GLA-SE), boosts IgG2c:IgG1 ratios, enhances hemagglutination inhibition (HAI) titers, and increases protection in aged mice...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29515583/k63-linked-polyubiquitination-on-traf6-regulates-lps-mediated-mapk-activation-cytokine-production-and-bacterial-clearance-in-toll-like-receptor-7-8-primed-murine-macrophages
#20
Jaya Talreja, Lobelia Samavati
Post viral infection bacterial pneumonia is a major cause of morbidity and mortality associated with both seasonal and pandemic influenza virus illness. Despite much efforts put into the discovery of mechanisms of post viral-bacterial infections and their complications in recent years, the molecular mechanisms underlying the increased susceptibility to bacterial infection remain poorly understood. In this study, we focused on the pathways regulating immune responses in murine macrophages and modeled post viral-bacterial infections through pretreatment of bone marrow-derived macrophages (BMDMs) with a toll-like receptor (TLR) 7/8 ligand (R848) and subsequent challenge with TLR2/4 agonists to mimic bacterial infection...
2018: Frontiers in Immunology
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