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https://www.readbyqxmd.com/read/28651122/activation-of-irf3-contributes-to-ifn-%C3%AE-and-isg54-expression-during-the-immune-responses-to-b16f10-tumor-growth
#1
Zachary Guinn, Deborah M Brown, Thomas M Petro
Interferon Regulatory Factor (IRF-3) has been shown to contribute to immune control of B16 melanoma tumor growth. We have shown previously that IRF-3 has a role in IFN-γ-induced expression of pro-apoptotic interferon stimulated gene 54 (ISG54) in macrophages and IFN-γ in T cells. To investigate the IRF3-IFN-γ-ISG54 nexus, we injected C57Bl/6 (B6) and IRF3KO mice s.c. with luciferase-producing B16-F10 tumor cells. Tumor growth as measured by luciferase levels was similar between B6 and IRF3KO mice at days 2 and 6, but was significantly greater at day 9 in IRF3KO mice compared with B6 mice...
June 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28646884/the-increased-concentration-of-macrophage-migration-inhibitory-factor-in-serum-and-cerebrospinal-fluid-of-patients-with-tick-borne-encephalitis
#2
Sambor Grygorczuk, Miłosz Parczewski, Renata Świerzbińska, Piotr Czupryna, Anna Moniuszko, Justyna Dunaj, Maciej Kondrusik, Sławomir Pancewicz
BACKGROUND: Host factors determining the clinical presentation of tick-borne encephalitis (TBE) are not fully elucidated. The peripheral inflammatory response to TBE virus is hypothesized to facilitate its entry into central nervous system by disrupting the blood-brain barrier with the involvement of a signaling route including Toll-like receptor 3 (TLR3) and pro-inflammatory cytokines macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNFα), and interleukin-1 beta (IL-1β)...
June 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28646209/upregulation-of-circulating-microrna-134-in-adult-onset-still-s-disease-and-its-use-as-potential-biomarker
#3
Tsai-Ling Liao, Yi-Ming Chen, Chia-Wei Hsieh, Hsin-Hua Chen, Hsiu-Chin Lee, Wei-Ting Hung, Kuo-Tung Tang, Der-Yuan Chen
Adult-onset Still's disease (AOSD) is a multi-systemic inflammatory disorder of unknown etiology. To date, no single diagnostic test is available for AOSD. Herein, we investigated the pathogenic role of microRNAs in AOSD. MicroRNA profiles in plasma from AOSD patients and healthy controls were analyzed by microarray analysis, followed by quantitative reverse transcription PCR validation. The biological functions of microRNAs were evaluated using in vitro cell-based assay. Among the differentially expressed microRNAs, microRNA-134 (miR-134) expression was positively correlated with AOSD activity scores and significantly decreased after effective treatment...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637878/cd4-t-cell-and-nk-cell-interplay-key-to-regression-of-mhc-class-i-low-tumors-upon-tlr7-8-agonist-therapy
#4
Elien M Doorduijn, Marjolein Sluijter, Daniela C Salvatori, Serenella Silvestri, Saskia Maas, Ramon Arens, Ferry Ossendorp, Sjoerd H van der Burg, Thorbald van Hall
One of the next challenges in cancer immunotherapy is the resistance of tumors to T cell-based treatments through loss of MHC class I. Here, we show that under these circumstances, the Toll-like receptor (TLR)-7/8 ligand imiquimod, but not the TLR3 ligand poly I:C or TLR9 ligand CpG, mediated an effective antitumor response. The rejection of these immune-escaped cancers was mediated by NK cells and CD4(+) T cells, whereas activated CD8(+) T cells were dispensable. Application of the innate immune stimulator at a distant site activated NK cells and thereby elicited tumor-specific T-cell responses in tumor-bearing mice...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28630328/toll-like-receptor-pathway-evolution-in-deuterostomes
#5
Michael G Tassia, Nathan V Whelan, Kenneth M Halanych
Animals have evolved an array of pattern-recognition receptor families essential for recognizing conserved molecular motifs characteristic of pathogenic microbes. One such family is the Toll-like receptors (TLRs). On pathogen binding, TLRs initiate specialized cytokine signaling catered to the class of invading pathogen. This signaling is pivotal for activating adaptive immunity in vertebrates, suggesting a close evolutionary relationship between innate and adaptive immune systems. Despite significant advances toward understanding TLR-facilitated immunity in vertebrates, knowledge of TLR pathway evolution in other deuterostomes is limited...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28626766/involvement-of-the-toll-like-receptor-nitric-oxide-signaling-pathway-in-the-pathogenesis-of-cervical-cancer-caused-by-high-risk-human-papillomavirus-infection
#6
Jie Li, Heping Rao, Chang'e Jin, Jinrong Liu
Human papillomavirus (HPV) can activate Toll-like receptor (TLR)/nitric oxide (NO) signaling pathways; however, whether the TLR/NO pathway is involved in cervical cancer caused by high-risk HPV (HR-HPV) remains unclear. In this study, 43 HR-HPV-positive patients with cervical cancer (CC group), 39 HR-HPV-positive patients with a healthy cervix (HR-HPV group), and 33 HR-HPV-negative controls were recruited. NO concentration in cervical canal and expression of inducible NO synthase (iNOS) in cervical tissues were detected...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28621230/lncrna-crnde-triggers-inflammation-through-the-tlr3-nf-%C3%AE%C2%BAb-cytokine-signaling-pathway
#7
Haowen Li, Qi Li, Tao Guo, Wenyan He, Chengya Dong, Yajie Wang
Colorectal neoplasia differentially expressed (CRNDE), an oncogene, is highly expressed in many tumor cells and affects cellular proliferation, migration, invasion, and apoptosis. Its function and mechanism of action is a research hotspot. In this study, microarray analysis was performed to discover the differentially expressed genes in CRNDE over-expression cells. RT² Profiler PCR Array was used to study the expression of genes related to the toll-like receptor (TLR) pathway. We found that over-expression of CRNDE in astrocytes increased the expression of key factors in the toll-like receptor signaling pathway, especially toll-like receptor-3-mediated MyD88-independent pathway...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28620261/single-nucleotide-polymorphism-based-genetic-diversity-analysis-of-the-kilakarsal-and-vembur-sheep-breeds
#8
Rathinasamy Selvam, Nagarajan Murali, A Kannan Thiruvenkadan, Ramesh Saravanakumar, Gurusamy Ponnudurai, Thilak Pon Jawahar
AIM: The present study was thus undertaken to analyze the genetic diversity of Kilakarsal and Vembur sheep breeds using single-nucleotide polymorphism (SNP) markers within Toll-like receptor (TLR) 3, 5, 6, 9, and 10 genes. MATERIALS AND METHODS: Competitive allele-specific polymerase chain reaction (PCR)-based end-point genotyping was performed using real-time PCR to type the SNPs. Allele discrimination module implemented in real-time PCR was utilized to call the genotypes based on fluorescence intensity recorded for each of the two alleles...
May 2017: Veterinary World
https://www.readbyqxmd.com/read/28617991/interferon-%C3%AE-regulates-the-production-of-il-10-by-toll-like-receptor-activated-microglia
#9
Diogo Lobo-Silva, Guilhermina M Carriche, A Gil Castro, Susana Roque, Margarida Saraiva
Pattern recognition receptors, such as toll-like receptors (TLRs), perceive tissue alterations and initiate local innate immune responses. Microglia, the resident macrophages of the brain, encode TLRs which primary role is to protect the tissue integrity. However, deregulated activation of TLRs in microglia may lead to chronic neurodegeneration. This double role of microglial responses is often reported in immune-driven neurologic diseases, as in multiple sclerosis (MS). Consequently, strategies to manipulate microglia inflammatory responses may help to ameliorate disease progression...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28607148/autophagy-downstream-of-endosomal-toll-like-receptors-signaling-in-macrophages-is-a-key-mechanism-for-resistance-to-leishmania-major-infection
#10
Luis H Franco, Anna K A Fleuri, Nat Aacutelia C Pellison, Gustavo F S Quirino, Catarina V Horta, Renan V H de Carvalho, Sérgio C Oliveira, Dario S Zamboni
Leishmaniasis is caused by protozoan parasites of the genus Leishmania. In mammalians, these parasites survive and replicate in macrophages and parasite elimination by macrophages is critical for host resistance. Endosomal Toll-like receptors (TLRs) have been shown to be crucial for resistance to L. major in vivo. For example, mice in the resistant C57BL/6 genetic background that are triple-deficient for TLR3, -7 and -9 (Tlr3/7/9-/-) are highly susceptible to L. major infection. Tlr3/7/9-/- mice are as susceptible as mice deficient in MyD88 or UNC93B1, a chaperone required for appropriate localization of endosomal TLRs, but the mechanisms are unknown...
June 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28602740/protective-immunity-against-rock-bream-iridovirus-rbiv-infection-and-tlr3-mediated-type-i-interferon-signaling-pathway-in-rock-bream-oplegnathus-fasciatus-following-poly-i-c-administration
#11
Myung-Hwa Jung, Sung-Ju Jung
In this study, we evaluated the potential of poly (I:C) to induce antiviral status for protecting rock bream from RBIV infection. Rock bream injected with poly (I:C) at 2 days before infection (1.1 × 10(4)) at 20 °C had significantly higher protection with RPS 13.4% and 33.4% at 100 and 200 μg/fish, respectively, through 100 days post infection (dpi). The addition of boost immunization with poly (I:C) at before/post infection at 20 °C clearly enhanced the level of protection showing 33.4% and 60.0% at 100 and 200 μg/fish, respectively...
June 8, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28601925/enhanced-stimulation-of-human-tumor-specific-t-cells-by-dendritic-cells-matured-in-the-presence-of-interferon-%C3%AE-and-multiple-toll-like-receptor-agonists
#12
Tanja Lövgren, Dhifaf Sarhan, Iva Truxová, Bhavesh Choudhary, Roeltje Maas, Jeroen Melief, Maria Nyström, Ulrika Edbäck, Renee Vermeij, Gina Scurti, Michael Nishimura, Giuseppe Masucci, Alex Karlsson-Parra, Andreas Lundqvist, Lars Adamson, Rolf Kiessling
Dendritic cell (DC) vaccines have been demonstrated to elicit immunological responses in numerous cancer immunotherapy trials. However, long-lasting clinical effects are infrequent. We therefore sought to establish a protocol to generate DC with greater immunostimulatory capacity. Immature DC were generated from healthy donor monocytes by culturing in the presence of IL-4 and GM-CSF and were further differentiated into mature DC by the addition of cocktails containing different cytokines and toll-like receptor (TLR) agonists...
June 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28592890/polymorphism-in-the-gene-encoding-toll-like-receptor-10-may-be-associated-with-asthma-after-bronchiolitis
#13
Sari Törmänen, Matti Korppi, Johanna Teräsjärvi, Juho Vuononvirta, Petri Koponen, Merja Helminen, Qiushui He, Kirsi Nuolivirta
Toll-like receptors (TLRs) recognise microbes that contribute to the severity of bronchiolitis and the subsequent risk of asthma. We evaluated whether post-bronchiolitis asthma was associated with polymorphisms in the TLR3 rs3775291, TLR4 rs4986790, TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084, and TLR10 rs4129009 genes. The gene polymorphisms were studied at the age of 6.4 years (mean) in 135 children hospitalised for bronchiolitis in infancy. The outcome measure was current or previous asthma. Current asthma was more common (30%) in children with the variant AG or GG genotype in the TLR10 rs4129009 gene versus those who were homozygous for the major allele A (11%) (p = 0...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588282/comparison-and-immunobiological-characterization-of-retinoic-acid-inducible-gene-i-like-receptor-expression-in-mesenchymal-stromal-cells
#14
Gordana Raicevic, Mehdi Najar, Hélène Busser, Emerence Crompot, Dominique Bron, Michel Toungouz, Laurence Lagneaux
Due to their immunomodulatory and regenerative properties, Mesenchymal stromal cells (MSC) have generated major interests in several clinical settings including transplantation and inflammatory diseases. MSC functions can be influenced by their tissue origin. Their microenvironment strongly affects their biology notably through TLR sensing. In this study, we show that MSC isolated from four different sources express another type of cytosolic pathogen recognition receptors known as retinoic acid inducible gene-I (RIG-I)-like receptors (RLR)...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28571545/potential-medications-or-compounds-acting-on-toll-like-receptors-in-cerebral-ischemia
#15
Man Li, Jing Liu, Ying Bi, Jixiang Chen, Lei Zhao
Toll-like receptors have been suggested to play an integral role in the process of inflammatory response after ischemic injury. Of all 9 TLRs presenting in brain, functions of TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 have been studied in recent years. The MyD88 pathway and TIR domain-containing adaptor inducing interferon pathway are involved in these pathophysiological changes. Since the important role, the therapeutic potential of strategies acting on TLRs should be evaluated. Feasible approaches may function in the following respects, methods acting on TLRs directly, modulations of MyD88 or TRIF signaling pathway, and the ischemic tolerance induced by the preconditioning or postconditioning with TLR ligands or minor cerebral ischemia...
June 1, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28570013/toll-like-receptor-2-antagonists-identified-through-virtual-screening-and-experimental-validation
#16
Prasannavenkatesh Durai, Hyeon-Jun Shin, Asma Achek, Hyuk-Kwon Kwon, Rajiv Gandhi Govindaraj, Suresh Panneerselvam, Dhanusha Yesudhas, Jiwon Choi, Kyoung Tai No, Sangdun Choi
Toll-like receptor 2 (TLR2) antagonists are key therapeutic targets because they inhibit several inflammatory diseases caused by surplus TLR2 activation. In this study, we identified two novel non-peptide TLR2 antagonists, C11 and C13, through pharmacophore-based virtual screening. At 10 μM, the level of interleukin-8 inhibition by C13 and C11 in human embryonic kidney TLR2 overexpressing cells is comparable to the commercially available TLR2 inhibitor CU-CPT22. In addition, C11 and C13 act in mouse macrophage-like RAW 264...
June 1, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28566380/seneca-valley-virus-suppresses-host-type-i-interferon-production-by-targeting-adaptor-proteins-mavs-trif-and-tank-for-cleavage
#17
Suhong Qian, Wenchun Fan, Tingting Liu, Mengge Wu, Huawei Zhang, Xiaofang Cui, Yun Zhou, Junjie Hu, Shaozhong Wei, Huanchun Chen, Xiangmin Li, Ping Qian
Seneca Valley Virus (SVV) is an oncolytic RNA virus belonging to the Picornaviridae family. Its nucleotide sequence is highly similar to those of members of the Cardiovirus genus. SVV is also a neuroendocrine cancer-selective oncolytic picornavirus that can be used for anti-cancer therapy. However, the interaction between SVV and its host is yet to be fully characterized. In this study, SVV inhibited antiviral type I interferon (IFN) responses by targeting different host adaptors, including mitochondrial anti-viral signaling (MAVS), Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF), and TRAF family member-associated NF-κB activator (TANK) via viral 3C(pro) SVV 3C(pro) mediated the cleavage of MAVS, TRIF, and TANK at specific sites, which required its protease activity...
May 31, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28565836/the-immune-mechanism-of-intestinal-tract-toll-like-receptor-in-mediating-ev71-virus-type-severe-hand-foot-and-mouth-disease-and-the-mapk-pathway
#18
Lei Zhu, Weihua Li, Gongjian Qi, Na Liu, Liping Sheng, Lei Shang, Boxiang Qi
Immunological response is thought to play a crucial role in the development of a severe hand-foot-and-mouth disease (HFMD) infection in children, but the mechanisms remain largely unknown. This study was designed to help in elucidating the immunopathological pathways involved in the disease by quantifying Toll-like receptor (TLR) mRNAs, MAPK factors and cytokine levels in children experiencing the disease. A total of 86 enterovirus 71 (EV71)-infected HFMD children (49 with mild and 27 with severe disease), along with 30 healthy children were involved in the study...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28564605/a-tlr3-specific-adjuvant-relieves-innate-resistance-to-pd-l1-blockade-without-cytokine-toxicity-in-tumor-vaccine-immunotherapy
#19
Yohei Takeda, Keisuke Kataoka, Junya Yamagishi, Seishi Ogawa, Tsukasa Seya, Misako Matsumoto
Cancer patients having anti-programmed cell death-1 (PD-1)/PD ligand 1 (L1)-unresponsive tumors may benefit from advanced immunotherapy. Double-stranded RNA triggers dendritic cell (DC) maturation to cross-prime antigen-specific cytotoxic T lymphocytes (CTLs) via Toll-like receptor 3 (TLR3). The TLR3-specific RNA agonist, ARNAX, can induce anti-tumor CTLs without systemic cytokine/interferon (IFN) production. Here, we have developed a safe vaccine adjuvant for cancer that effectively implements anti-PD-L1 therapy...
May 30, 2017: Cell Reports
https://www.readbyqxmd.com/read/28562479/sepsis-up-regulates-cd14-expression-in-a-myd88-dependent-and-trif-independent-pathway
#20
Zhixia Chen, Zhenzhen Shao, Shuya Mei, Zhengzheng Yan, Xibing Ding, Timothy Billiar, Quan Li
An overwhelming immune response, particularly from macrophages, plays a critical role in survival and organ damage in sepsis patients. TLRs are important receptors to recognize the conserved motifs expressed by invading bacteria. The TLRs except TLR3 signal via a MyD88 dependent pathway. TLR3 uses a TRIF dependent pathway, while TLR4 uses both MyD88 and TRIF dependent pathways. Previous studies indicated that CD14 was necessary for TLRs dependent production of pro-inflammatory cytokines. Blocking CD14 protected against the deleterious systemic inflammatory response associated with sepsis...
May 29, 2017: Shock
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