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https://www.readbyqxmd.com/read/28515281/cxcl4-exposure-potentiates-tlr-driven-polarization-of-human-monocyte-derived-dendritic-cells-and-increases-stimulation-of-t-cells
#1
Sandra C Silva-Cardoso, Alsya J Affandi, Lotte Spel, Marta Cossu, Joel A G van Roon, Marianne Boes, Timothy R D J Radstake
Chemokines have been shown to play immune-modulatory functions unrelated to steering cell migration. CXCL4 is a chemokine abundantly produced by activated platelets and immune cells. Increased levels of circulating CXCL4 are associated with immune-mediated conditions, including systemic sclerosis. Considering the central role of dendritic cells (DCs) in immune activation, in this article we addressed the effect of CXCL4 on the phenotype and function of monocyte-derived DCs (moDCs). To this end, we compared innate and adaptive immune responses of moDCs with those that were differentiated in the presence of CXCL4...
May 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28506291/targeting-cd22-with-the-monoclonal-antibody-epratuzumab-modulates-human-b-cell-maturation-and-cytokine-production-in-response-to-toll-like-receptor-7-tlr7-and-b-cell-receptor-bcr-signaling
#2
Natalia V Giltiay, Geraldine L Shu, Anthony Shock, Edward A Clark
BACKGROUND: Abnormal B-cell activation is implicated in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). The B-cell surface molecule CD22, which regulates activation through the B-cell receptor (BCR), is a potential target for inhibiting pathogenic B cells; however, the regulatory functions of CD22 remain poorly understood. In this study, we determined how targeting of CD22 with epratuzumab (Emab), a humanized anti-CD22 IgG1 monoclonal antibody, affects the activation of human B-cell subsets in response to Toll-like receptor 7 (TLR7) and BCR engagement...
May 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28502294/-resiquimod-r848-has-more-stronger-immune-adjuvantivity-than-other-tested-tlr-agonists
#3
Yuan Shen, Menghua Zeng, Feng Qiu, Hua Tang
Objective To compare and characterize the Th1 immune responses induced by the most commonly used commercial Toll-like receptor (TLR) agonists through in vivo and ex vivo experiments. Methods The concentrations of IL-12 were tested by ELISA after mouse dendritic cells (DCs) in vitro were stimulated by one of tested TLR agonists, including poly(I:C), monophosphoryl lipid A (MPLA), resiquimod (R848), cytosine polyguanine-C (CpG-C). The changes in percentage and phenotype of DCs, NK cells and effector T cells in the draining lymph nodes were analyzed by flow cytometry after BALB/c mice were immunized with ovalbumin (OVA) mixed with selected TLR agonist...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28495370/an-optimized-method-for-enumerating-cns-derived-memory-b-cells-during-viral-induced-inflammation
#4
Krista D DiSano, Stephen A Stohlman, Cornelia C Bergmann
BACKGROUND: CNS inflammation resulting from infection, injury, or neurodegeneration leads to accumulation of diverse B cell subsets. Although antibody secreting cells (ASC) within the inflamed CNS have been extensively examined, memory B cell (Bmem) characterization has been limited as they do not secrete antibody without stimulation. Moreover, unlike human Bmem, reliable surface markers for murine Bmem remain elusive. NEW METHOD: Using a viral encephalomyelitis model we developed a modified limiting dilution in vitro stimulation assay to convert CNS-derived virus specific Bmem into ASC...
May 8, 2017: Journal of Neuroscience Methods
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
#5
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/28394395/effects-of-inhibitors-of-transcription-factors-nuclear-factor-%C3%AE%C2%BAb-and-activator-protein-1-on-the-expression-of-proinflammatory-cytokines-and-chemokines-induced-by-stimulation-with-toll-like-receptor-ligands-in-hen-vaginal-cells
#6
T Kamimura, N Isobe, Y Yoshimura
The goal of this study was to determine whether nuclear factor-κB (NFκB) and activator protein 1 (AP-1) were the responsible transcription factors for the induction of proinflammatory cytokines in hen vaginal cells stimulated by different Toll-like receptor (TLR) ligands. Cultured vaginal cells were treated with or without poly I:C (TLR3 ligand; dsRNA virus), lipopolysaccharide (LPS) (TLR4 ligand; gram-negative bacteria), flagellin (TLR5 ligand; bacterial flagellum), R848 (TLR7 ligand; ssRNA virus), and CpG-oligodeoxynucleotide (CpG-ODN) (TLR21 ligand; bacteria and DNA virus) in the presence or absence of different doses of BAY11-7085 (NFκB inhibitor) and tanshinone IIA (AP-1 inhibitor)...
March 1, 2017: Poultry Science
https://www.readbyqxmd.com/read/28386554/identification-of-ifitm1-and-ifitm3-in-goose-gene-structure-expression-patterns-and-immune-reponses-against-tembusu-virus-infection
#7
Anqi Wang, Lipei Sun, Mingshu Wang, Renyong Jia, Dekang Zhu, Mafeng Liu, Kunfeng Sun, Qiao Yang, Ying Wu, Xiaoyue Chen, Anchun Cheng, Shun Chen
As interferon-stimulated genes (ISGs), interferon-inducible transmembrane proteins 1 and 3 (IFITM1 and IFITM3) can effectively inhibit the replication of multiple viruses. Here, goose IFITM1 and IFITM3 were cloned and identified for the first time. The two proteins share the same topological structure and several important sites critical for the antiviral functions in other species are conserved in the goose. Goose IFITM1 and IFITM3 are most closely related to their respective orthologs in ducks; these proteins exhibited high mRNA transcript levels in immune-related tissues, including the thymus, bursa of Fabricius, and Harderian gland, compared to other tissues...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28363108/a-novel-small-molecule-compound-possesses-immunomodulatory-properties-on-bone-marrow-derived-dendritic-cells-via-tlr7-signaling-pathway-and-alleviates-the-development-of-sle
#8
Sheng Gao, Linbo Yuan, Cunyu Li, Liping Han, Chunyan Hua
Dendritic cells (DCs) play an important role in the development and maintenance of immune tolerance. Activation of TLR7, which is expressed in DCs, is thought to contribute to the complex pathophysiology of systemic lupus erythematosus (SLE). In this study, we analyzed the in vitro and in vivo function of a novel small-molecule compound, FC-99, which was previously reported to have immunomodulatory functions. We found that FC-99 inhibited the expression of CD40 and inflammatory mediators (IL-6, IL-12, and CXCL-10), as well as R848-induced phosphorylation of IκB-α...
March 28, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28339016/paeonol-ameliorates-imiquimod-induced-psoriasis-like-skin-lesions-in-balb-c-mice-by-inhibiting-the-maturation-and-activation-of-dendritic-cells
#9
Yujiao Meng, Mingxing Wang, Xiangjiang Xie, Tingting Di, Jingxia Zhao, Yan Lin, Xiaolong Xu, Ningfei Li, Yating Zhai, Yan Wang, Ping Li
Paeonol, an active component derived from the traditional Chinese medicine Cortex Moutan, possesses anti-inflammatory, analgesic, antioxidant and anti-allergic properties. Psoriasis is a chronic, recurrent, inflammatory dermatosis accompanied by excessive activation of Toll‑like receptors (TLRs) in dendritic cells (DCs), which are primarily responsible for initiating an immune response. We investigated the effect of paeonol on inflammation in an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated by R848...
May 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28323387/induction-of-tumor-regression-by-intratumoral-sting-agonists-combined-with-anti-programmed-death-l1-blocking-antibody-in-a-preclinical-squamous-cell-carcinoma-model
#10
Shekhar K Gadkaree, Juan Fu, Rupashree Sen, Michael J Korrer, Clint Allen, Young J Kim
BACKGROUND: Cyclic dinucleotides (CDNs) are bacterial intracellular messengers that have demonstrated antitumor activity in melanoma and breast tumors, although their role in immunotherapy of head and neck squamous cell cancers (HNSCCs) has not been well investigated. METHODS: We measured primary tumor growth rates, mechanism of antitumor activity, and efficacy of programmed death-L1 blockade combinatorial therapy in SCCFVII tumor-bearing C3H/HeOUJ mice undergoing intratumoral injections with RR-cyclic-di-guanine (synthetic CDG), CDG (natural cyclic-di-guanine), R848 (TLR 7/8 agonist), or phosphate buffered saline (PBS, control)...
March 21, 2017: Head & Neck
https://www.readbyqxmd.com/read/28268194/a-bioluminescent-caspase-1-activity-assay-rapidly-monitors-inflammasome-activation-in-cells
#11
Martha O'Brien, Danielle Moehring, Raúl Muñoz-Planillo, Gabriel Núñez, Justin Callaway, Jenny Ting, Mike Scurria, Tim Ugo, Laurent Bernad, James Cali, Dan Lazar
Inflammasomes are protein complexes induced by diverse inflammatory stimuli that activate caspase-1, resulting in the processing and release of cytokines, IL-1β and IL-18, and pyroptosis, an immunogenic form of cell death. To provide a homogeneous method for detecting caspase-1 activity, we developed a bioluminescent, plate-based assay that combines a substrate, Z-WEHD-aminoluciferin, with a thermostable luciferase in an optimized lytic reagent added directly to cultured cells. Assay specificity for caspase-1 is conferred by inclusion of a proteasome inhibitor in the lytic reagent and by use of a caspase-1 inhibitor to confirm activity...
March 6, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28115243/intravaginal-immunisation-using-a-novel-antigen-releasing-ring-device-elicits-robust-vaccine-antigen-specific-systemic-and-mucosal-humoral-immune-responses
#12
Paul F McKay, Jamie F S Mann, Aditya Pattani, Vicky Kett, Yoann Aldon, Deborah King, R Karl Malcolm, Robin J Shattock
The generation of effective levels of antigen-specific immunity at the mucosal sites of pathogen entry is a key goal for vaccinologists. We explored topical vaginal application as an approach to initiate local antigen-specific immunity, enhance previously existing systemic immunity or re-target responses to the mucosae. To deliver a protein vaccine formulation to the vaginal mucosal surface, we used a novel vaginal ring device comprising a silicone elastomer body into which three freeze-dried, rod-shaped, hydroxypropylmethylcellulose inserts were incorporated...
March 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28072760/pentoxifylline-inhibits-tlr-and-inflammasome-mediated-in-vitro-inflammatory-cytokine-production-in-human-blood-with-greater-efficacy-and-potency-in-newborns
#13
Esther M Speer, David J Dowling, Lukasz S Ozog, Jianjin Xu, Jie Yang, Geetika Kennady, Ofer Levy
BACKGROUND: Toll-like receptor (TLR)-mediated inflammation may contribute to neonatal sepsis, for which pentoxifylline (PTX), a phosphodiesterase inhibitor that raises intracellular cAMP, is a candidate adjunctive therapy. We characterized the anti-inflammatory effects of PTX toward TLR-mediated production of inflammatory (tumor necrosis factor (TNF) and interleukin (IL)-1β) and proresolution (IL-6 and IL-10) cytokines in human newborn and adult blood. METHODS: Newborn cord and adult blood were treated with PTX (50-400 µmol/l) before, during or after stimulation with LPS (TLR4 agonist), R848 (TLR7/8 agonist) or LPS/ATP (inflammasome activation)...
May 2017: Pediatric Research
https://www.readbyqxmd.com/read/28069966/inherited-human-irak-1-deficiency-selectively-impairs-tlr-signaling-in-fibroblasts
#14
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/28024872/molecular-and-functional-characterization-of-pigeon-columba-livia-tumor-necrosis-factor-receptor-associated-factor-3
#15
Yingying Zhou, Xilong Kang, Dan Xiong, Shanshan Zhu, Huijuan Zheng, Ying Xu, Yaxin Guo, Zhiming Pan, Xinan Jiao
Tumor necrosis factor receptor-associated factor 3 (TRAF3) plays a key antiviral role by promoting type I interferon production. We cloned the pigeon TRAF3 gene (PiTRAF3) according to its predicted mRNA sequence to investigate its function. The 1704-bp full-length open reading frame encodes a 567-amino acid protein. One Ring finger, two TRAF-type Zinc fingers, one Coiled coil, and one MATH domain were inferred. RT-PCR showed that PiTRAF3 was expressed in all tissues, with relatively weak expression in the heart and liver...
December 23, 2016: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/27999742/reprogramming-of-tlr7-signaling-enhances-antitumor-nk-and-cytotoxic-t-cell-responses
#16
Christian Hotz, Marina Treinies, Ines Mottas, Laurin C Rötzer, Anne Oberson, Lorenzo Spagnuolo, Maurizio Perdicchio, Thibaud Spinetti, Tina Herbst, Carole Bourquin
Toll-like receptor (TLR) 7 agonists are effective in topical application for the immunotherapy of skin cancers, but their performance for the systemic treatment of solid tumors is limited by the development of TLR tolerance. In this study, we describe a novel strategy to overcome TLR tolerance and enhance TLR7-dependent antitumor immune responses through reprogramming of TLR signaling pathways. The sensitivity of TLR7 signaling in dendritic cells (DC) was increased by prior stimulation with the dsRNA poly(I:C) that mimics virally induced immune activation...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27999739/tlr7-based-cancer-immunotherapy-decreases-intratumoral-myeloid-derived-suppressor-cells-and-blocks-their-immunosuppressive-function
#17
Thibaud Spinetti, Lorenzo Spagnuolo, Inès Mottas, Chiara Secondini, Marina Treinies, Curzio Rüegg, Christian Hotz, Carole Bourquin
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells with the capacity to inhibit immunological responses. During cancer progression, MDSC are recruited to the tumor sites and secondary lymphoid organs, leading to the suppression of the antitumor function of NK and T cells. Here, we show that the TLR7/8 agonist resiquimod (R848) has a direct effect on MDSC populations in tumor-bearing mice. Systemic application of R848 led to a rapid reduction in both intratumoral and circulating MDSC...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27995135/trim25-identification-in-the-chinese-goose-gene-structure-tissue-expression-profiles-and-antiviral-immune-responses-in-vivo-and-in-vitro
#18
Yunan Wei, Hao Zhou, Anqi Wang, Lipei Sun, Mingshu Wang, Renyong Jia, Dekang Zhu, Mafeng Liu, Qiao Yang, Ying Wu, Kunfeng Sun, Xiaoyue Chen, Anchun Cheng, Shun Chen
The retinoic acid-inducible gene I (RIG-I) and the RIG-I-like receptor (RLR) protein play a critical role in the interferon (IFN) response during RNA virus infection. The tripartite motif containing 25 proteins (TRIM25) was reported to modify caspase activation and RIG-I recruitment domains (CARDs) via ubiquitin. These modifications allow TRIM25 to interact with mitochondrial antiviral signaling molecules (MAVs) and form CARD-CARD tetramers. Goose TRIM25 was cloned from gosling lungs, which possess a 1662 bp open reading flame (ORF)...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27905985/tlr7-8-agonist-induces-a-post-entry-samhd1-independent-block-to-hiv-1-infection-of-monocytes
#19
Henning Hofmann, Bénédicte Vanwalscappel, Nicolin Bloch, Nathaniel R Landau
BACKGROUND: Monocytes, the primary myeloid cell-type in peripheral blood, are resistant to HIV-1 infection as a result of the lentiviral restriction factor SAMHD1. Toll-like receptors recognize microbial pathogen components, inducing the expression of antiviral host proteins and proinflammatory cytokines. TLR agonists that mimic microbial ligands have been found to have activity against HIV-1 in macrophages. The induction of restriction factors in monocytes by TLR agonist activation has not been well studied...
December 1, 2016: Retrovirology
https://www.readbyqxmd.com/read/27890931/a-tlr7-agonist-enhances-the-antitumor-efficacy-of-obinutuzumab-in-murine-lymphoma-models-via-nk-cells-and-cd4-t-cells
#20
E J Cheadle, G Lipowska-Bhalla, S J Dovedi, E Fagnano, C Klein, J Honeychurch, T M Illidge
Anti-CD20 monoclonal antibodies (mAb) such as rituximab have been proven to be highly effective at improving outcome in B-cell malignancies. However, many patients ultimately relapse and become refractory to treatment. The glycoengineered anti-CD20 mAb obinutuzumab was developed to induce enhanced antibody-dependent cellular cytotoxicity, antibody-dependent phagocytosis and direct cell death and was shown to lead to improved outcomes in a randomized study in B-CLL. We hypothesized that immune stimulation through Toll-like receptor 7 (TLR7) agonism in combination with obinutuzumab would further enhance lymphoma clearance and the generation of long-term antitumor immune responses...
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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