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https://www.readbyqxmd.com/read/28228336/evaluation-of-hydrophobic-chitosan-based-particulate-formulations-of-porcine-reproductive-and-respiratory-syndrome-virus-vaccine-candidate-t-cell-antigens
#1
Helen Mokhtar, Lucia Biffar, Satyanarayana Somavarapu, Jean-Pierre Frossard, Sarah McGowan, Miriam Pedrera, Rebecca Strong, Jane C Edwards, Margarita Garcia-Durán, Maria Jose Rodriguez, Graham R Stewart, Falko Steinbach, Simon P Graham
PRRS control is hampered by the inadequacies of existing vaccines to combat the extreme diversity of circulating viruses. Since immune clearance of PRRSV infection may not be dependent on the development of neutralising antibodies and the identification of broadly-neutralising antibody epitopes have proven elusive, we hypothesised that conserved T cell antigens represent potential candidates for development of a novel PRRS vaccine. Previously we had identified the M and NSP5 proteins as well-conserved targets of polyfunctional CD8 and CD4 T cells...
February 3, 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28228119/genetic-variation-of-the-toll-like-receptors-in-a-swedish-allergic-rhinitis-case-population
#2
V Henmyr, D Carlberg, E Manderstedt, C Lind-Halldén, T Säll, L O Cardell, C Halldén
BACKGROUND: Variation in the 10 toll-like receptor (TLR) genes has been significantly associated with allergic rhinitis (AR) in several candidate gene studies and three large genome-wide association studies. These have all investigated common variants, but no investigations for rare variants (MAF ≤ 1%) have been made in AR. The present study aims to describe the genetic variation of the promoter and coding sequences of the 10 TLR genes in 288 AR patients. METHODS: Sanger sequencing and Ion Torrent next-generation sequencing was used to identify polymorphisms in a Swedish AR population and these were subsequently compared and evaluated using 1000Genomes and Exome Aggregation Consortium (ExAC) data...
February 23, 2017: BMC Medical Genetics
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/28219705/substance-p-represents-a-novel-first-line-defense-mechanism-in-the-nose
#4
Olivia Larsson, Lotta Tengroth, Yuan Xu, Rolf Uddman, Susanna Kumlien Georén, Lars-Olaf Cardell
BACKGROUND: Neuropeptides, such as substance P (SP), have long been seen as mediators of widespread, continuous airway inflammation, a process known as neurogenic inflammation. However, this has been difficult to demonstrate clinically, suggesting an alternative role for these signaling molecules. OBJECTIVES: To examine the role of SP in nasal infection, by assessing the release of SP in response to viral stimulation and characterizing the effects of SP on innate immunity, the latter reflected in changes in local Toll-like receptor (TLR) expression...
February 17, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28218976/differential-expression-of-innate-immune-response-genes-in-clinical-phases-of-chronic-hepatitis-b-infection
#5
Sara Romani, Seyed Masoud Hosseini, Seyed Reza Mohebbi, Andre Boonstra, Afsaneh Sharifian
We investigated innate immune gene expression in clinical phases of Chronic Hepatitis B infection, including immune tolerant (IT); immune active (IA); inactive carrier (IC); and hepatitis B e antigen (HBeAg)-negative phases, as well as healthy controls. Expression levels of interferon types I, II, and III, their receptor subunits, IRFs, TLRs and other IFN-induced genes in peripheral blood mononuclear cells were compared.Forty HBsAg-positive treatment-naïve subjects without co-infection with HIV, HCV or HDV were enrolled...
February 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28212561/the-tlr7-agonist-imiquimod-induces-anti-cancer-effects-via-autophagic-cell-death-and-enhances-anti-tumoral-and-systemic-immunity-during-radiotherapy-for-melanoma
#6
Jeong Hyun Cho, Hyo-Ji Lee, Hyun-Jeong Ko, Byung-Il Yoon, Jongseon Choe, Keun-Cheol Kim, Tae-Wook Hahn, Jeong A Han, Sun Shim Choi, Young Mee Jung, Kee-Ho Lee, Yun-Sil Lee, Yu-Jin Jung
Toll-like receptor (TLR) ligands are strongly considered immune-adjuvants for cancer immunotherapy and have been shown to exert direct anti-cancer effects. This study was performed to evaluate the synergistic anti-cancer and anti-metastatic effects of the TLR7 agonist imiquimod (IMQ) during radiotherapy for melanoma. The pretreatment of B16F10 or B16F1 cells with IMQ combined with γ-ionizing radiation (IR) led to enhanced cell death via autophagy, as demonstrated by increased expression levels of autophagy-related genes, and an increased number of autophagosomes in both cell lines...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209121/evolution-of-toll-like-receptors-in-the-context-of-terrestrial-ungulates-and-cetaceans-diversification
#7
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/28199419/early-immune-responses-and-development-of-pathogenesis-of-avian-infectious-bronchitis-viruses-with-different-virulence-profiles
#8
Cintia Hiromi Okino, Marcos Antônio Zanella Mores, Iara Maria Trevisol, Arlei Coldebella, Hélio José Montassier, Liana Brentano
Avian infectious bronchitis virus (IBV) primarily replicates in epithelial cells of the upper respiratory tract of chickens, inducing both morphological and immune modulatory changes. However, the association between the local immune responses induced by IBV and the mechanisms of pathogenesis has not yet been completely elucidated. This study compared the expression profile of genes related to immune responses in tracheal samples after challenge with two Brazilian field isolates (A and B) of IBV from the same genotype, associating these responses with viral replication and with pathological changes in trachea and kidney...
2017: PloS One
https://www.readbyqxmd.com/read/28197384/oncolytic-measles-virus-induces-tumor-necrosis-factor-related-apoptosis-inducing-ligand-trail-mediated-cytotoxicity-by-human-myeloid-and-plasmacytoid-dendritic-cells
#9
Carole Achard, Jean-Baptiste Guillerme, Daniela Bruni, Nicolas Boisgerault, Chantal Combredet, Frédéric Tangy, Nolwenn Jouvenet, Marc Grégoire, Jean-François Fonteneau
Attenuated measles virus (MV) is currently being evaluated in clinical trials as an oncolytic therapeutic agent. Originally used for its lytic activity against tumor cells, it is now admitted that the effectiveness of MV also lies in its ability to initiate antitumor immune responses through the activation of dendritic cells (DCs). In this study, we investigated the capacity of oncolytic MV to convert human blood myeloid CD1c(+) DCs and plasmacytoid DCs (pDCs) into cytotoxic effectors. We found that MV induces the expression of the cytotoxic protein TNF-related apoptosis-inducing ligand (TRAIL) on the surface of DCs...
2017: Oncoimmunology
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/28179531/toll-like-receptor-7-agonist-gs-9620-induces-hiv-expression-and-hiv-specific-immunity-in-cells-from-hiv-infected-individuals-on-suppressive-antiretroviral-therapy
#11
Angela Tsai, Alivelu Irrinki, Jasmine Kaur, Tomas Cihlar, George Kukolj, Derek D Sloan, Jeffrey P Murry
Antiretroviral therapy can suppress HIV replication to undetectable levels but does not eliminate latent HIV, thus necessitating lifelong therapy. Recent efforts to target this persistent reservoir have focused on inducing the expression of latent HIV so that infected cells may be recognized and eliminated by the immune system. Toll like receptor (TLR) activation stimulates antiviral immunity and has been shown to induce HIV from latently infected cells. Activation of TLR7 leads to the production of several stimulatory cytokines, including type I interferons (IFNs)...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28170444/impaired-toll-like-receptor-7-and-9-induced-immune-activation-in-chronic-spinal-cord-injured-patients-contributes-to-immune-dysfunction
#12
Gozde Gucluler, Emre Adiguzel, Bilgi Gungor, Tamer Kahraman, Mayda Gursel, Bilge Yilmaz, Ihsan Gursel
Reduced immune activation or immunosuppression is seen in patients withneurological diseases. Urinary and respiratory infections mainly manifested as septicemia and pneumonia are the most frequent complications following spinal cord injuries and they account for the majority of deaths. The underlying reason of these losses is believed to arise due to impaired immune responses to pathogens. Here, we hypothesized that susceptibility to infections of chronic spinal cord injured (SCI) patients might be due to impairment in recognition of pathogen associated molecular patterns and subsequently declining innate and adaptive immune responses that lead to immune dysfunction...
2017: PloS One
https://www.readbyqxmd.com/read/28168735/does-imiquimod-pretreatment-optimize-308-nm-excimer-laser-uvb-therapy-in-psoriasis-patients
#13
Joselin D Tacastacas, Patricia Oyetakin-White, David C Soler, Andrew Young, Sarah Groft, Kord Honda, Kevin D Cooper, Thomas S McCormick
Psoriasis continues to be a debilitating skin disease affecting 1-3% of the United States population. Although the effectiveness of several current biologic therapies have described this pathology as a IL-23, TNF-α and Th17-mediated disease, less invasive approaches are still in use and in need of refinement. One of these is the usage of narrow band-UVB (NB-UVB) therapy to deplete specifically intra-epidermal CD3(+) , CD4(+) and CD8(+) cells to clear psoriatic plaques. In order to improve NB-UVB therapy, we sought to determine whether skin pre-treatment with the TLR7 agonist imiquimod (IMQ) would help increase the efficiency of the former at resolving psoriatic plaques...
February 7, 2017: Photodermatology, Photoimmunology & Photomedicine
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
#14
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/28159900/serum-mir-29a-is-upregulated-in-acute-graft-versus-host-disease-and-activates-dendritic-cells-through-tlr-binding
#15
Parvathi Ranganathan, Apollinaire Ngankeu, Nina C Zitzer, PierPaolo Leoncini, Xueyan Yu, Lucia Casadei, Kishore Challagundla, Dawn K Reichenbach, Sabrina Garman, Amy S Ruppert, Stefano Volinia, Jessica Hofstetter, Yvonne A Efebera, Steven M Devine, Bruce R Blazar, Muller Fabbri, Ramiro Garzon
Acute graft-versus-host disease (aGVHD) continues to be a frequent and devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT), posing as a significant barrier against the widespread use of HSCTs as a curative modality. Recent studies suggested serum/plasma microRNAs (miRs) may predict aGVHD onset. However, little is known about the functional role of circulating miRs in aGVHD. In this article, we show in two independent cohorts that miR-29a expression is significantly upregulated in the serum of allogeneic HSCT patients at aGVHD onset compared with non-aGVHD patients...
February 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28153581/delivery-of-tlr7-agonist-to-monocytes-and-dendritic-cells-by-dcir-targeted-liposomes-induces-robust-production-of-anti-cancer-cytokines
#16
Thomas C B Klauber, Janne M Laursen, Daniel Zucker, Susanne Brix, Simon S Jensen, Thomas L Andresen
: Tumor immune escape is today recognized as an important cancer hallmark and is therefore a major focus area in cancer therapy. Monocytes and dendritic cells (DCs), which are central to creating a robust anti-tumor immune response and establishing an anti-tumorigenic microenvironment, are directly targeted by the tumor escape mechanisms to develop immunosuppressive phenotypes. Providing activated monocytes and DCs to the tumor tissue is therefore an attractive way to break the tumor-derived immune suppression and reinstate cancer immune surveillance...
January 30, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28146629/identification-of-high-potency-human-tlr8-and-dual-tlr7-tlr8-agonists-in-pyrimidine-2-4-diamines
#17
Mallesh Beesu, Alex C D Salyer, Michael J H Brush, Kathryn L Trautman, Justin K Hill, Sunil A David
The induction of Toll-like receptor 7 (TLR7)-dependent Type I interferons (IFN-α/β) from plasmacytoid dendritic cells as well as the production of TLR8-dependent Type II interferon (IFN-γ), TNF-α, and IL-12 in myeloid dendritic cells are of importance in generating T helper-1 biased adaptive immune responses. In an effort to identify novel dual TLR7/TLR8-active compounds, we undertook structure-activity relationship studies in pyrimidine 2,4-diamines, focusing on substituents at C5. Several analogues substituted with aminopropyl appendages at C5 displayed dominant TLR8-agonistic activity...
February 1, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28134982/%C3%AE-synuclein-induces-microglial-cell-migration-through-stimulating-hif-1%C3%AE-accumulation
#18
Hongfei Qiao, Xijing He, Qiaojun Zhang, Ni Zhang, Libo Li, Yanping Hui, Wenjuan Li, Dong Wang, Zhonghen Wu
Microglial cell migration and infiltration plays a critical role in spinal cord injury after thoracoabdominal aortic surgery. In our previous study, α-synuclein, a presynaptic protein was shown to be released from injured neurons and cause microglial cell activation. Here, we aimed to explore the effect of α-synuclein on microglial cell migration. Primary microglial cells were isolated from Sprague-Dawley rats and then exposed different doses (0.2, 0.4, and 0.6 μM) of α-synuclein oligomers. The mRNA and protein levels of HIF-1α were then analyzed by qRT-PCR and Western blot...
January 30, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28131813/microrna-146a-induction-during-influenza-h3n2-virus-infection-targets-and-regulates-traf6-levels-in-human-nasal-epithelial-cells-hnecs
#19
Yuqin Deng, Yan Yan, Kai Sen Tan, Jing Liu, Vincent T Chow, Ze-Zhang Tao, De-Yun Wang
We have previously shown that human nasal epithelial cells (hNECs) are highly permissive cells for respiratory viruses including influenza A virus (IAV) and respiratory syncytial virus. Recent studies have indicated that microRNAs (miRNAs) are involved in virus-host relationship, and this led us to investigate its essential roles in the in vitro hNECs model derived from multiple donors. By comparing the differential expression of miRNAs upon IAV infection among animal and cell line studies, candidates were selected with focus on the initial immune response...
January 25, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28122964/circulating-and-exosome-packaged-hepatitis-c-single-stranded-rna-induce-monocyte-differentiation-via-tlr7-8-to-polarized-macrophages-and-fibrocytes
#20
Banishree Saha, Karen Kodys, Adeyinka Adejumo, Gyongyi Szabo
Monocytes and macrophages (MΦs) play a central role in the pathogenesis of chronic hepatitis C virus (HCV) infection. The tissue microenvironment triggers monocyte differentiation into MΦs, with polarization ranging within the spectrum of M1 (classical) to M2 (alternative) activation. Recently, we demonstrated that HCV infection leads to monocyte differentiation into polarized MΦs that mediate stellate cell activation via TGF-β. In this study, we aimed to identify the viral factor(s) that mediate monocyte-to-MΦ differentiation...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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