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https://www.readbyqxmd.com/read/28224203/nucleic-acid-sensing-pattern-recognition-receptors-in-the-development-of-colorectal-cancer-and-colitis
#1
REVIEW
Liangmei He, Yayun Chen, Yuanbing Wu, Ying Xu, Zixiang Zhang, Zhiping Liu
Colorectal cancer (CRC) is a leading cause of cancer-related deaths that is often associated with inflammation initiated by activation of pattern recognition receptors (PRRs). Nucleic acid sensing PRRs are one of the major subsets of PRRs that sense nucleic acid (DNA and RNA), mainly including some members of Toll-like receptors (TLR3, 7, 8, 9), AIM2-like receptors (AIM2, IFI16), STING, cGAS, RNA polymerase III, and DExD/H box nucleic acid helicases (such as RIG-I like receptors (RIG-I, MDA5, LPG2), DDX1, 3, 5, 7, 17, 21, 41, 60, and DHX9, 36)...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28223987/dendritic-cell-targeting-effectively-boosts-t-cell-responses-elicited-by-an-hiv-multiepitope-dna-vaccine
#2
Juliana de Souza Apostólico, Victória Alves Santos Lunardelli, Marcio Massao Yamamoto, Higo Fernando Santos Souza, Edecio Cunha-Neto, Silvia Beatriz Boscardin, Daniela Santoro Rosa
Despite several efforts in the last decades, an efficacious HIV-1 vaccine is still not available. Different approaches have been evaluated, such as recombinant proteins, viral vectors, DNA vaccines, and, most recently, dendritic cell (DC) targeting. This strategy is based on DC features that place them as central for induction of immunity. Targeting is accomplished by the use of chimeric monoclonal antibodies directed to DC surface receptors fused to the antigen of interest. In this work, we targeted eight promiscuous HIV-derived CD4(+) T cell epitopes (HIVBr8) to the DEC205(+) DCs by fusing the multiepitope immunogen to the heavy chain of αDEC205 (αDECHIVBr8), in the presence of the TLR3 agonist poly (I:C)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28223111/expression-analysis-of-nine-toll-like-receptors-in-yellow-catfish-pelteobagrus-fulvidraco-responding-to-aeromonas-hydrophila-challenge
#3
Xiao-Ting Zhang, Gui-Rong Zhang, Ze-Chao Shi, Yu-Jie Yuan, Huan Zheng, Li Lin, Kai-Jian Wei, Wei Ji
Toll-like receptors (TLRs) are important components of pattern recognition receptors (PRRs), which play significant roles in innate immunity to defense against pathogen invasion. Many TLRs have been found in teleosts, but there are no reports about cloning and expression of TLR genes in yellow catfish (Pelteobagrus fulvidraco). In this study, we analyzed the sequence characters and the relative mRNA expression levels of nine TLRs (TLR1, TLR2, TLR3, TLR4-1, TLR5, TLR7, TLR8-2, TLR9 and TLR22) in different tissues of yellow catfish...
February 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28211536/expression-profiling-of-trim-protein-family-in-thp1-derived-macrophages-following-tlr-stimulation
#4
Mei-Xiu Jiang, Xuan Hong, Bin-Bin Liao, Shui-Zhen Shi, Xiao-Fang Lai, Huai-Yu Zheng, Lin Xie, Yuan Wang, Xiao-Lei Wang, Hong-Bo Xin, Mingui Fu, Ke-Yu Deng
Activated macrophages play an important role in many inflammatory diseases including septic shock and atherosclerosis. However, the molecular mechanisms limiting macrophage activation are not completely understood. Members of the tripartite motif (TRIM) family have recently emerged as important players in innate immunity and antivirus. Here, we systematically analyzed mRNA expressions of representative TRIM molecules in human THP1-derived macrophages activated by different toll-like receptor (TLR) ligands. Twenty-nine TRIM members were highly induced (>3 fold) by one or more TLR ligands, among which 19 of them belong to TRIM C-IV subgroup...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209713/mir-718-represses-pro-inflammatory-cytokine-production-through-targeting-pten
#5
Parisa Kalantari, Omid F Harandi, Sarika Agarwal, Florentina Rus, Evelyn A Kurt-Jones, Katherine A Fitzgerald, Daniel R Caffrey, Douglas T Golenbock
Bacterial sepsis involves a complex interaction between the host immune response and bacterial lipopolysaccharides (LPS). LPS binds Toll-like receptor (TLR) 4, which leads to the release of pro-inflammatory cytokines that are essential for a potent innate immune response against pathogens. The innate immune system is tightly regulated as excessive inflammation can lead to organ failure and death. MicroRNAs have recently emerged as important regulators of the innate immune system. Here, we determined the function of miR-718, which is conserved across mammals and overlaps with the 5 UTR of the Interleukin-1 Receptor-Associated Kinase (IRAK1) gene...
February 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28209121/evolution-of-toll-like-receptors-in-the-context-of-terrestrial-ungulates-and-cetaceans-diversification
#6
Edson Ishengoma, Morris Agaba
BACKGROUND: Toll-like receptors (TLRs) are the frontline actors in the innate immune response to various pathogens and are expected to be targets of natural selection in species adapted to habitats with contrasting pathogen burdens. The recent publication of genome sequences of giraffe and okapi together afforded the opportunity to examine the evolution of selected TLRs in broad range of terrestrial ungulates and cetaceans during their complex habitat diversification. Through direct sequence comparisons and standard evolutionary approaches, the extent of nucleotide and protein sequence diversity in seven Toll-like receptors (TLR2, TLR3, TLR4, TLR5, TLR7, TLR9 and TLR10) between giraffe and closely related species was determined...
February 16, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28202935/polymorphisms-of-toll-like-receptors-2-and-9-and-severity-and-prognosis-of-bacterial-meningitis-in-chinese-children
#7
Pingping Zhang, Nan Zhang, Linlin Liu, Kai Zheng, Liang Zhu, Junping Zhu, Lina Cao, Yiyuan Jiang, Gang Liu, Qiushui He
Toll-like receptors (TLRs) play a crucial role in innate immunity, protecting the host from bacterial pathogens. We investigated whether bacterial meningitis (BM) in children was associated with gene polymorphisms in TLR2 (rs3804099), TLR3 (rs3775291 and rs3775290) and TLR9 (rs352139 and rs352140). Blood samples were taken from 218 child patients with confirmed BM and 330 healthy adult controls (HC) and polymorphisms of these genes were analyzed by PCR-based sequencing. For TLR2 rs3804099, frequencies of the minor allele C were markedly higher in patients with severe BM (defined as CSF glucose concentration ≤ 1...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202532/cd40-signaling-drives-potent-cellular-immune-responses-in-heterologous-cancer-vaccinations
#8
Supot Nimanong, Dmitrij Ostroumov, Jessica Wingerath, Sarah Knocke, Norman Woller, Engin Guerlevik, Christine Falk, Michael P Manns, Florian Kuehnel, Thomas C Wirth
Antagonistic antibodies targeting co-inhibitory receptors have revolutionized the treatment of cancer by inducing durable immune responses and clinical remissions in patients. In contrast, success of agonistic costimulatory antibodies has thus far been limited due to insufficient induction of adaptive immune responses. Here we describe a novel vaccination method consisting of a primary dendritic cell immunization followed by a composite vaccination including an agonistic CD40 antibody, soluble antigen and a TLR3 agonist, referred to as CoAT...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28198368/tlr4-signaling-induces-tlr3-up-regulation-in-alveolar-macrophages-during-acute-lung-injury
#9
Xibing Ding, Shuqing Jin, Yao Tong, Xi Jiang, Zhixia Chen, Shuya Mei, Liming Zhang, Timothy R Billiar, Quan Li
Acute lung injury is a life-threatening inflammatory response caused by severe infection. Toll-like receptors in alveolar macrophages (AMΦ) recognize the molecular constituents of pathogens and activate the host's innate immune responses. Numerous studies have documented the importance of TLR-TLR cross talk, but few studies have specifically addressed the relationship between TLR4 and TLR3. We explored a novel mechanism of TLR3 up-regulation that is induced by LPS-TLR4 signaling in a dose- and time-dependent manner in AMΦ from C57BL/6 mice, while the LPS-induced TLR3 expression was significantly reduced in TLR4(-/-) and Myd88(-/-) mice and following pretreatment with a NF-κB inhibitor...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196735/gtl001-and-bivalent-cyaa-based-therapeutic-vaccine-strategies-against-human-papillomavirus-and-other-tumor-associated-antigens-induce-effector-and-memory-t-cell-responses-that-inhibit-tumor-growth
#10
Michaël Esquerré, Marie Momot, Anne Goubier, Christophe Gonindard, Stéphane Leung-Theung-Long, Yolande Misseri, Marie-Christine Bissery
GTL001 is a bivalent therapeutic vaccine containing human papillomavirus (HPV) 16 and HPV18 E7 proteins inserted in the Bordetella pertussis adenylate cyclase (CyaA) vector intended to prevent cervical cancer in HPV-infected women with normal cervical cytology or mild abnormalities. To be effective, therapeutic cervical cancer vaccines should induce both a T cell-mediated effector response against HPV-infected cells and a robust CD8(+) T-cell memory response to prevent potential later infection. We examined the ability of GTL001 and related bivalent CyaA-based vaccines to induce, in parallel, effector and memory CD8(+) T-cell responses to both vaccine antigens...
February 10, 2017: Vaccine
https://www.readbyqxmd.com/read/28194022/multifaceted-roles-of-trim38-in-innate-immune-and-inflammatory-responses
#11
REVIEW
Ming-Ming Hu, Hong-Bing Shu
The tripartite motif-containing (TRIM) proteins represent the largest E3 ubiquitin ligase family. The multifaceted roles of TRIM38 in innate immunity and inflammation have been intensively investigated in recent years. TRIM38 is essential for cytosolic RNA or DNA sensor-mediated innate immune responses to both RNA and DNA viruses, while negatively regulating TLR3/4- and TNF/IL-1β-triggered inflammatory responses. In these processes, TRIM38 acts as an E3 ubiquitin or SUMO ligase, which targets key cellular signaling components, or as an enzymatic activity-independent regulator...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28167945/tlr7-and-tlr3-sense-brucella-abortus-rna-to-induce-proinflammatory-cytokine-production-but-they-are-dispensable-for-host-control-of-infection
#12
Priscila C Campos, Marco Túlio R Gomes, Erika S Guimarães, Gabriela Guimarães, Sergio C Oliveira
Brucella abortus is a Gram-negative, facultative intracellular bacterium that causes brucellosis, a worldwide zoonotic disease leading to undulant fever in humans and abortion in cattle. The immune response against this bacterium relies on the recognition of microbial pathogen-associated molecular patterns, such as lipoproteins, lipopolysaccharides, and DNA; however, the immunostimulatory potential of B. abortus RNA remains to be elucidated. Here, we show that dendritic cells (DCs) produce significant amounts of IL-12, IL-6, and IP-10/CXCL10, when stimulated with purified B...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28166799/toll-like-receptor-3-activation-selectively-reverses-hiv-latency-in-microglial-cells
#13
David Alvarez-Carbonell, Yoelvis Garcia-Mesa, Stephanie Milne, Biswajit Das, Curtis Dobrowolski, Roxana Rojas, Jonathan Karn
BACKGROUND: Multiple toll-like receptors (TLRs) are expressed in cells of the monocytic lineage, including microglia, which constitute the major reservoir for human immunodeficiency virus (HIV) infection in the brain. We hypothesized that TLR receptor mediated responses to inflammatory conditions by microglial cells in the central nervous system (CNS) are able to induce latent HIV proviruses, and contribute to the etiology of HIV-associated neurocognitive disorders. RESULTS: Newly developed human microglial cell lines (hµglia), obtained by immortalizing human primary microglia with simian virus-40 (SV40) large T antigen and the human telomerase reverse transcriptase, were used to generate latently infected cells using a single-round HIV virus carrying a green fluorescence protein reporter (hµglia/HIV, clones HC01 and HC69)...
February 6, 2017: Retrovirology
https://www.readbyqxmd.com/read/28166388/toll-like-receptor-3-deficiency-decreases-epileptogenesis-in-a-pilocarpine-model-of-se-induced-epilepsy-in-mice
#14
Adi Gross, Felix Benninger, Ravit Madar, Tomer Illouz, Kathleen Griffioen, Israel Steiner, Daniel Offen, Eitan Okun
OBJECTIVE: Epilepsy affects 60 million people worldwide. Despite the development of antiepileptic drugs, up to 35% of patients are drug refractory with uncontrollable seizures. Toll-like receptors (TLRs) are central components of the nonspecific innate inflammatory response. Because TLR3 was recently implicated in neuronal plasticity, we hypothesized that it may contribute to the development of epilepsy after status epilepticus (SE). METHODS: To test the involvement of TLR3 in epileptogenesis, we used the pilocarpine model for SE in TLR3-deficient mice and their respective wild-type controls...
February 6, 2017: Epilepsia
https://www.readbyqxmd.com/read/28159912/identification-of-tbk1-complexes-required-for-the-phosphorylation-of-irf3-and-the-production-of-interferon-b
#15
Siddharth Bakshi, Jordan Taylor, Sam Strickson, Thomas Macartney, Philip Cohen
The double-stranded RNA mimetic poly(I:C) and LPS activate Toll-like Receptor 3 (TLR3) and TLR4, respectively, triggering the activation of TANK-Binding Kinase 1 (TBK1) complexes, the phosphorylation of Interferon Regulatory Factor 3 (IRF3) and transcription of the Interferon b (IFNb) gene. Here, we demonstrate that the TANK-TBK1 and Optineurin (OPTN)-TBK1 complexes control this pathway. The poly(I:C)- or LPS-stimulated phosphorylation of IRF3 at Ser396 and production of IFNb were greatly reduced in bone-marrow-derived macrophages (BMDM) from TANK knock-out (KO) mice crossed to knock-in mice-expressing the ubiquitin-binding-defective OPTN[D477N] mutant...
February 3, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28152141/toll-like-receptor-3-activation-initiates-photoreceptor-cell-death-in-vivo-and-in-vitro
#16
Mei-Ling Gao, Kun-Chao Wu, Wen-Li Deng, Xin-Lan Lei, Lue Xiang, Gao-Hui Zhou, Chun-Yun Feng, Xue-Wen Cheng, Chang-Jun Zhang, Feng Gu, Rong-Han Wu, Zi-Bing Jin
Purpose: Accumulating evidence has demonstrated that excessive immunoreaction plays a prominent role in the pathogenesis of dry AMD. Toll-like receptor 3 (TLR3) can be activated by double-stranded (ds)RNA in retinal pigment epithelia and trigger an innate immunity-mediated inflammatory response. However, its role in photoreceptor cells, the effectors of AMD geographic atrophy, remains unclear. Methods: The expression of TLR3 was examined in mouse retina and in a murine photoreceptor cell line (661W)...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28150518/chloroquine-attenuates-tlr3-ifn-%C3%AE-signaling-in-cultured-normal-human-mesangial-cells-a-possible-protective-effect-against-renal-damage-in-lupus-nephritis
#17
Tadaatsu Imaizumi, Ryo Hayakari, Tomoh Matsumiya, Hidemi Yoshida, Kazushi Tsuruga, Shojiro Watanabe, Shogo Kawaguchi, Hiroshi Tanaka
BACKGROUND: Chloroquine has been reported to protect against renal damage in lupus nephritis (LN), however, its detailed mechanism in glomerular inflammation remains unclear. Upregulation of the type I interferon (IFN) system plays a pivotal role in LN pathogenesis, therefore, we examined whether chloroquine inhibits Toll-like receptor 3 (TLR3)/IFN-β signaling in cultured normal human mesangial cells (MCs). METHODS: We examined chloroquine effect on the representative TLR3/IFN-β signaling axis, TLR3/IFN-β/retinoic acid-inducible gene-I (RIG-I)/CCL5 in MCs treated with polyinosinic-polycytidylic acid (poly IC), a synthetic viral dsRNA analog and analyzed the expression of these molecules using reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay...
February 2, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28149670/expression-and-regulation-of-cholecystokinin-receptor-in-the-chicken-s-immune-organs-and-cells
#18
Seham El-Kassas, Solomon Odemuyiwa, George Hajishengallis, Terry D Connell, Toufic O Nashar
Cholecystokinin (CCK) is a neuropeptide that affects growth rate in chickens by regulating appetite. CCK peptides exert their function by binding to two identified receptors, CCKAR and CCKBR in the GI tract and the brain, respectively, as well as in other organs. In mammals, CCK/CCKAR interactions affect a number of immunological parameters, including regulation of lymphocytes and functioning of monocytes. Thus, food intake and growth can potentially be altered by infection and the resulting inflammatory immune response...
December 2016: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/28148965/rapid-detection-of-functional-gene-polymorphisms-of-tlrs-and-il-17-using-high-resolution-melting-analysis
#19
Johanna Teräsjärvi, Antti Hakanen, Matti Korppi, Kirsi Nuolivirta, Kirsi Gröndahl-Yli-Hannuksela, Jussi Mertsola, Ville Peltola, Qiushui He
Genetic variations in toll-like receptors (TLRs) and IL-17A have been widely connected to different diseases. Associations between susceptibility and resistance to different infections and single nucleotide polymorphisms (SNPs) in TLR1 to TLR4 and IL17A have been found. In this study, we aimed to develop a rapid and high throughput method to detect functional SNPs of above mentioned proteins. The following most studied and clinically important SNPs: TLR1 (rs5743618), TLR2 (rs5743708), TLR3 (rs3775291), TLR4 (rs4986790) and IL17 (rs2275913) were tested...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28143806/efficient-eradication-of-established-tumors-in-mice-with-cationic-liposome-based-synthetic-long-peptide-vaccines
#20
Eleni Maria Varypataki, Naomi Benne, Joke Bouwstra, Wim Jiskoot, Ferry Ossendorp
Therapeutic vaccination with synthetic long peptides (SLPs) can be clinically effective against HPV-induced pre-malignant lesions; however, their efficiency in established malignant lesions leaves room for improvement. Here, we report the high therapeutic potency of cationic liposomes loaded with well-defined tumor-specific SLPs and a TLR3 ligand as adjuvant. The cationic particles, with an average size of 160 nm, could strongly activate functional, antigen-specific, CD8(+) and CD4(+) T cells and induced in vivo cytotoxicity against target cells after intradermal vaccination...
January 31, 2017: Cancer Immunology Research
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