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https://www.readbyqxmd.com/read/28439271/cross-talk-between-inhibitory-immunoreceptor-tyrosine-based-activation-motif-signaling-and-toll-like-receptor-pathways-in-macrophages-and-dendritic-cells
#1
REVIEW
Ivan Hirsch, Vaclav Janovec, Ruzena Stranska, Nathalie Bendriss-Vermare
The innate immune cells sense microbial infection and self-ligands by pathogen recognition receptors (PRRs), such as toll-like receptors (TLRs) and regulatory receptors (RRs), associated with immunoreceptor tyrosine-based activation motif (ITAM). Rapid activation and concerted action of PRRs signaling and feedback inhibitory mechanisms must be engaged to ensure the host defense functions and to prevent cytotoxicity associated with excessive activation. ITAM-associated RRs can generate stimulatory or, paradoxically, inhibitory signals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28439064/immunotherapy-of-dual-function-vector-with-both-immunostimulatory-and-b-cell-lymphoma-2-bcl-2-silencing-effects-on-gastric-carcinoma
#2
Lanying Ma, Mei Han, Zumureti Keyoumu, Hua Wang, Saifuding Keyoumu
BACKGROUND Tumorigenesis is a kind of pathology marked by infinite proliferation and restrained apoptosis compared with normal cells. The abnormal expression of some proto-oncogenes and apoptosis inhibition are essential for tumor growth, which has been confirmed by molecular biologic and immunologic studies. The hypofunction of the host immune system also drives the development and metastasis of malignant tumors. Bcl-2, which has a critical role in regulating apoptosis, is overexpressed in several cancers...
April 25, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28437629/design-and-development-of-benzoxazole-derivatives-with-toll-like-receptor-9-antagonism
#3
Swarnali Roy, Ayan Mukherjee, Barnali Paul, Oindrila Rahaman, Shounak Roy, Gundaram Maithri, Bandaru Ramya, Sourav Pal, Dipyaman Ganguly, Arindam Talukdar
Toll-like receptor 9 (TLR9) is a major therapeutic target for numerous inflammatory disorders. Development of small molecule inhibitors for TLR9 remains largely empirical due to lack of structural understanding of potential TLR9 antagonism by small molecules and due to the unusual topology of the ligand binding surface of the receptor. To develop a structural model for rational design of small molecule TLR9 antagonists, an enhanced homology model of human TLR9 (hTLR9) was constructed. Binding mode analysis of a series of molecules having characteristic molecular geometry, flexibility and basicity was conducted based on crystal structure of the inhibitory DNA (iDNA) bound to horse and bovine TLR9...
April 5, 2017: European Journal of Medicinal Chemistry
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
#4
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
#5
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
#6
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/28422377/intraperitoneal-gardiquimod-protects-against-hepatotoxicity-through-inhibition-of-oxidative-stress-and-inflammation-in-mice-with-sepsis
#7
Suqian Guo, Yu Zhang, Zhifen Wang, Yonghao Yu, Guolin Wang
Many reports recapitulate the contribution of reactive oxygen species (ROS) over-accumulation to the organ damage; it is of significance to strictly target ROS production. In this study, we evaluated the potential role of TLR7 agonist gardiquimod (GDQ) in oxidative stress (OS) in liver injury induced by sepsis. Here, we observed that intraperitoneal pretreatment with GDQ dramatically elevated the septic survival rate and effectively attenuated the septic liver injury. Interestingly, the increased ROS and inflammatory factor IL-6 levels were reversed after GDQ intervention...
April 19, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28419514/activition-of-tlr7-inhibition-of-mycobacterium-tuberculosis-survival-by-autophagy-in-raw-264-7-macrophages
#8
Meng Bao, Zhengjun Yi, Yurong Fu
The aim of the study was to evaluate the effect of regulation of TLR7 on Mycobacterium tuberculosis (Mtb) survival in macrophages. TLR7 expression in macrophages infected by Mtb was detected by RT-PCR and western blotting. Regulation of TLR7 was achieved by single strand RNA (ssRNA) or siRNA. The effects of TLR7 on Mtb survival and cell viability were detected by acid fast staining and cell counting kit-8, respectively. Cell ultrastructure was observed via transmission electron microscopy (TEM), and autophagy related protein LC3 was analyzed by western blotting...
April 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28416650/epigenetic-regulator-cxxc5-recruits-dna-demethylase-tet2-to-regulate-tlr7-9-elicited-ifn-response-in-pdcs
#9
Shixin Ma, Xiaoling Wan, Zihou Deng, Lei Shi, Congfang Hao, Zhenyuan Zhou, Chun Zhou, Yiyuan Fang, Jinghua Liu, Jing Yang, Xia Chen, Tiantian Li, Aiping Zang, Shigang Yin, Bin Li, Joel Plumas, Laurence Chaperot, Xiaoming Zhang, Guoliang Xu, Lubin Jiang, Nan Shen, Sidong Xiong, Xiaoming Gao, Yan Zhang, Hui Xiao
TLR7/9 signals are capable of mounting massive interferon (IFN) response in plasmacytoid dendritic cells (pDCs) immediately after viral infection, yet the involvement of epigenetic regulation in this process has not been documented. Here, we report that zinc finger CXXC family epigenetic regulator CXXC5 is highly expressed in pDCs, where it plays a crucial role in TLR7/9- and virus-induced IFN response. Notably, genetic ablation of CXXC5 resulted in aberrant methylation of the CpG-containing island (CGI) within the Irf7 gene and impaired IRF7 expression in steady-state pDCs...
April 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28408069/tlr7-mediated-activation-of-xbp1-correlates-with-the-ifn%C3%AE-production-in-humans
#10
Claudia Beisel, Susanne Ziegler, Glòria Martrus Zapater, Anaïs Chapel, Morgane Griesbeck, Heike Hildebrandt, Ansgar W Lohse, Marcus Altfeld
The transcription factor X-box binding protein 1 (XBP1) represents a key component of the endoplasmatic reticulum (ER) stress response and is required for the production of several pro-inflammatory cytokines. XBP1 is furthermore essential for the development and survival of plasmacytoid dendritic cells (pDCs), and has recently been suggested to be involved in toll-like receptor (TLR) 2/4 signaling. Activation of TLR7 on pDCs results in an upregulation of pro-inflammatory cytokines, such as type I interferons (IFN-I), and has been implicated in several autoimmune and inflammatory diseases, but the role of XBP1 in this process remains unknown...
April 10, 2017: Cytokine
https://www.readbyqxmd.com/read/28406067/rna-and-a-cell-wall-component-of-enterococcus-faecalis-ic-1-are-required-for-phagocytosis-and-interleukin-12-production-by-the-mouse-macrophage-cell-line-j774-1
#11
Junpei Nakase, Yuuichi Ukawa, Syoji Takemoto, Takayoshi Kubo, Yuko M Sagesaka, Ayako Aoki-Yoshida, Mamoru Totsuka
Enterococcus faecalis is a resident lactic acid bacterium in the human intestine. Its immunostimulatory action was reported to be enhanced by heat sterilization. To investigate its beneficial actions, we evaluated the ability of 10 E. faecalis strains to induce interleukin-12 (IL-12) production in a mouse macrophage cell line, J774.1 and found that the strain, E. faecalis IC-1, had a potent IL-12-inducing ability. Furthermore, we investigated the underlying mechanism by treating IC-1 cells with RNase or lysozyme...
April 13, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28405010/toll-like-receptor-7-deficiency-protects-apolipoprotein-e-deficient-mice-from-diet-induced-atherosclerosis
#12
Cong-Lin Liu, Marcela M Santos, Cleverson Fernandes, Mengyang Liao, Karine Iamarene, Jin-Ying Zhang, Galina K Sukhova, Guo-Ping Shi
Toll-like receptor 7 (TLR7) mediates autoantigen and viral RNA-induced cytokine production. Increased TLR7 expression in human atherosclerotic lesions suggests its involvement in atherogenesis. Here we demonstrated TLR7 expression in macrophages, smooth muscle cells (SMCs), and endothelial cells from mouse atherosclerotic lesions. To test a direct participation of TLR7 in atherosclerosis, we crossbred TLR7-deficient (Tlr7 (-/-)) mice with apolipoprotein E-deficient (Apoe (-/-)) mice and produced Apoe (-/-) Tlr7 (-/-) and Apoe (-/-) Tlr7 (+/+) littermates, followed by feeding them an atherogenic diet to produce atherosclerosis...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28403045/polymorphisms-of-mannose-binding-lectin-and-toll-like-receptors-2-3-4-7-and-8-and-the-risk-of-respiratory-infections-and-acute-otitis-media-in-children
#13
Laura Toivonen, Juho Vuononvirta, Jussi Mertsola, Matti Waris, Qiushui He, Ville Peltola
BACKGROUND: Mannose-binding lectin (MBL) and toll-like receptors (TLRs) are important components of the innate immune system. We assessed the susceptibility of children with genetic variants in these factors to respiratory infections, rhinovirus infections and acute otitis media. METHODS: In a prospective cohort study, blood samples from 381 Finnish children were analyzed for polymorphisms in MBL2 at codons 52, 54 and 57, TLR2 Arg753Gln, TLR3 Leu412Phe, TLR4 Asp299Gly, TLR7 Gln11Leu and TLR8 Leu651Leu...
May 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28400473/tlr-sensing-of-bacterial-spore-associated-rna-triggers-host-immune-responses-with-detrimental-effects
#14
Min-Kyung Choo, Yasuyo Sano, Changhoon Kim, Kei Yasuda, Xiao-Dong Li, Xin Lin, Mary Stenzel-Poore, Lena Alexopoulou, Sankar Ghosh, Eicke Latz, Ian R Rifkin, Zhijian J Chen, George C Stewart, Hyonyong Chong, Jin Mo Park
The spores of pathogenic bacteria are involved in host entry and the initial encounter with the host immune system. How bacterial spores interact with host immunity, however, remains poorly understood. Here, we show that the spores of Bacillus anthracis (BA), the etiologic agent of anthrax, possess an intrinsic ability to induce host immune responses. This immunostimulatory activity is attributable to high amounts of RNA present in the spore surface layer. RNA-sensing TLRs, TLR7, and TLR13 in mice and their human counterparts, are responsible for detecting and triggering the host cell response to BA spores, whereas TLR2 mediates the sensing of vegetative BA...
April 11, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28397237/-progress-in-research-on-tlr7-gene-single-nucleotide-polymorphisms-and-copy-number-variations-in-autoimmune-diseases
#15
Jianxiong Xi, Qiming Zhang, Yanfeng Zou
Autoimmune diseases (AID) are a group of complex disorders due to antibodies acting on self-antigens causing damage to the body. AID has long been considered as the outcome of genetic and environmental interactions. In recent years, studies have shown that increased susceptibility to AID may be associated with single nucleotide polymorphisms and copy number variations of Toll like receptor 7 (TLR7) gene, which provided a clue to further understanding of the pathogenesis of AID. This paper provides a review of the recent advances in understanding of the roles of TLR7 gene single nucleotide polymorphisms and copy number variations in AID...
April 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
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
#16
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/28392787/bioconjugation-of-small-molecules-to-rna-impedes-its-recognition-by-toll-like-receptor-7
#17
Isabell Hellmuth, Isabel Freund, Janine Schlöder, Salifu Seidu-Larry, Kathrin Thüring, Kaouthar Slama, Jens Langhanki, Stefka Kaloyanova, Tatjana Eigenbrod, Matthias Krumb, Sandra Röhm, Kalina Peneva, Till Opatz, Helmut Jonuleit, Alexander H Dalpke, Mark Helm
A fundamental mechanism of the innate immune system is the recognition, via extra- and intracellular pattern-recognition receptors, of pathogen-associated molecular patterns. A prominent example is represented by foreign nucleic acids, triggering the activation of several signaling pathways. Among these, the endosomal toll-like receptor 7 (TLR7) is known to be activated by single-stranded RNA (ssRNA), which can be specifically influenced through elements of sequence structure and posttranscriptional modifications...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28387980/immune-balance-in-hepatitis-b-infection-present-and-future-therapies
#18
REVIEW
Ashish Kumar Vyas, Ankur Jindal, Syed Hissar, Gayatri Ramakrishna, Nirupama Trehanpati
Chronic hepatitis B virus (HBV) infection affects millions of people worldwide and about half a million people die every year. India represents the second largest pool of chronic HBV infections with an estimated 40 million chronically infected patients. Persistence or clearance of HBV infection mainly depends upon host immune responses. Chronically infected individuals remain in immune tolerant phase unless HBV flares and leads to development of chronic active hepatitis or acute on chronic liver failure. Strategies based on inhibition of viral replication (nucleoside analogues) or immune modulation (Interferons) as monotherapy, or in combination in sequential therapies, are currently being used globally for reducing HBV viral load and mediating HBsAg clearance...
April 7, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28378808/distribution-location-and-transcriptional-profile-of-peyer-s-patch-conventional-dc-subsets-at-steady-state-and-under-tlr7-ligand-stimulation
#19
J Bonnardel, C Da Silva, C Wagner, R Bonifay, L Chasson, M Masse, E Pollet, M Dalod, J-P Gorvel, H Lelouard
The initiation of the mucosal immune response in Peyer's patch (PP) relies on the sampling, processing, and efficient presentation of foreign antigens by dendritic cells (DCs). Among PP DCs, CD11b(+) conventional DCs (cDCs) and lysozyme-expressing DCs (LysoDCs) have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here we show that both DN and CD11b(+) cDCs belong to a unique SIRPα(+) cDC subset...
April 5, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28374903/rna-sensors-of-the-innate-immune-system-and-their-detection-of-pathogens
#20
REVIEW
Nanhua Chen, Pengpeng Xia, Shuangjie Li, Tangjie Zhang, Tony T Wang, Jianzhong Zhu
The innate immune system plays a critical role in pathogen recognition and initiation of protective immune response through the recognition of pathogen associated molecular patterns (PAMPs) by its pattern recognition receptors (PRRs). Nucleic acids including RNA and DNA have been recognized as very important PAMPs of pathogens especially for viruses. RNA are the major PAMPs of RNA viruses, to which most severe disease causing viruses belong thus posing a tougher challenge to human and animal health. Therefore, the understanding of the immune biology of RNA PRRs is critical for control of pathogen infections especially for RNA virus infections...
April 4, 2017: IUBMB Life
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