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https://www.readbyqxmd.com/read/28814521/hiv-fusion-in-dendritic-cells-mainly-occurs-at-the-surface-and-is-limited-by-low-cd4-levels
#1
Lise Chauveau, Daniel Aaron Donahue, Blandine Monel, Francoise Porrot, Timothée Bruel, Lea Richard, Nicoletta Casartelli, Olivier Schwartz
HIV-1 poorly infects monocyte-derived dendritic cells (MDDCs). This is in a large part due to SAMHD1, which restricts viral reverse transcription. Pseudotyping HIV-1 with VSV-G strongly enhances infection, suggesting that earlier steps of viral replication, including fusion, are also inefficient in MDDCs. The site of HIV-1 fusion remains controversial and may depend on the cell type, with reports indicating that it occurs at the plasma membrane or contrarily, in an endocytic compartment. Here, we examined the pathways of HIV-1 entry in MDDCs...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28807280/immunization-with-inactivated-antigens-of-neospora-caninum-induces-toll-like-receptors-3-7-8-and-9-in-maternal-fetal-interface-of-infected-pregnant-heifers
#2
M S Marin, Y P Hecker, S Quintana, S E Pérez, M R Leunda, G J Cantón, E R Cobo, D P Moore, A C Odeón
Neospora caninum is an obligate parasite and a major cause of abortion in cattle. Pregnancy failures appear to be associated with weak innate defences on the maternal-fetal interface during infection with N. caninum. Herein, we studied the gene expression of Toll-like receptors (TLRs) in pregnant heifers immunized with different vaccine formulations against N. caninum before mating and then challenged the heifers with live N. caninum on day 70 of gestation. TLR7 and TLR8 expression was upregulated in the placental caruncle of infected-pregnant heifers previously exposed to live N...
August 30, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28806745/persistent-mycobacteria-evade-an-antibacterial-program-mediated-by-phagolysosomal-tlr7-8-myd88-in-human-primary-macrophages
#3
Alexandre Gidon, Signe Elisabeth Åsberg, Claire Louet, Liv Ryan, Markus Haug, Trude Helen Flo
Pathogenic mycobacteria reside in macrophages where they avoid lysosomal targeting and degradation through poorly understood mechanisms proposed to involve arrest of phagosomal maturation at an early endosomal stage. A clear understanding of how this relates to host defenses elicited from various intracellular compartments is also missing and can only be studied using techniques allowing single cell and subcellular analyses. Using confocal imaging of human primary macrophages infected with Mycobacterium avium (Mav) we show evidence that Mav phagosomes are not arrested at an early endosomal stage, but mature to a (LAMP1+/LAMP2+/CD63+) late endosomal/phagolysosomal stage where inflammatory signaling and Mav growth restriction is initiated through a mechanism involving Toll-like receptors (TLR) 7 and 8, the adaptor MyD88 and transcription factors NF-κB and IRF-1...
August 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28794025/retrovirus-based-virus-like-particle-immunogenicity-and-its-modulation-by-toll-like-receptor-activation
#4
Fabien Pitoiset, Thomas Vazquez, Beatrice Levacher, Djamel Nehar-Belaid, Nicolas Dérian, James Vigneron, David Klatzmann, Bertrand Bellier
Retrovirus-derived virus-like particles (VLPs) are particularly interesting vaccine platforms as they trigger efficient humoral and cellular immune responses and can be used to display heterologous antigens. In this study, we characterized the intrinsic immunogenicity of VLPs and investigated their possible adjuvantization by incorporation of toll-like receptor (TLR) ligands. We designed a non-coding single-stranded RNA (ncRNA) that could be encapsidated by VLPs and induce TLR7/8-signaling. We found that VLPs efficiently induce in vitro dendritic cell activation, which can be improved by ncRNA encapsidation (ncRNAVLPs)...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28783457/platelets-modulate-innate-immune-response-against-human-respiratory-syncytial-virus-in-vitro
#5
Vesla I Kullaya, Quirijn de Mast, Andre van der Ven, Hicham elMoussaoui, Gibson Kibiki, Elles Simonetti, Marien I de Jonge, Gerben Ferwerda
Detection of respiratory syncytial virus (RSV) in blood, including mononuclear leukocytes and organs other than the lung, suggests that RSV disseminates outside the respiratory tract. In this study, the role of platelets in host defense against RSV was explored using an in vitro model. Platelets, also produced in the lungs, are increasingly recognized as an important part of host immune responses and may therefore play a role in modulating lung infections and clearing RSV viremia. In human peripheral blood mononuclear cells (PBMCs), platelets significantly reduced RSV infection of monocytes, monocyte activation, and interferon (IFN)α/γ production...
August 7, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28777892/therapeutical-modulation-of-plasmacytoid-dendritic-cells-in-experimental-arthritis
#6
Ramzi Nehmar, Ghada Alsaleh, Benjamin Voisin, Vincent Flacher, Alexandre Mariotte, Victoria Saferding, Antonia Puchner, Birgit Niederreiter, Thierry Vandamme, Gernot Schabbauer, Philippe Kastner, Susan Chan, Peggy Kirstetter, Martin Holcmann, Christopher Mueller, Jean Sibilia, Seiamak Bahram, Stephan Blüml, Philippe Georgel
OBJECTIVES: The role of plasmacytoid dendritic cells (pDCs) and type I Interferons in rheumatoid arthritis (RA) remains controversial. To explore their contribution to RA pathogenesis, we induced experimental arthritis in various animal models of pDC depletion. We also monitored the effect of localized pDC recruitment and activation on joint inflammation and bone damage. METHODS: Experimental arthritis in mice was obtained by K/BxN serum transfer, heterologous collagen immunization (CIA) or in hTNF-transgenics...
August 4, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28768858/human-metapneumovirus-m2-2-protein-acts-as-a-negative-regulator-of-alpha-interferon-production-by-plasmacytoid-dendritic-cells
#7
Yoshinori Kitagawa, Madoka Sakai, Mariko Funayama, Masae Itoh, Bin Gotoh
Human metapneumovirus (HMPV) has the ability to inhibit TLR7- and TLR9-dependent alpha interferon (IFN-α) production by plasmacytoid dendritic cells (pDCs). However the inhibition mechanism remains largely unknown. To identify viral proteins responsible for this inhibition, we performed a screening of HMPV open reading frames (ORFs) for their abilities to block TLR7/9-dependent signaling reconstituted in HEK293T cells by transfection with MyD88, TRAF6, IKKα, and IRF7. This screening demonstrated that the M2-2 protein was the most potent inhibitor of TLR7/9-dependent IFN-α induction...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768728/extracellular-micrornas-induce-potent-innate-immune-responses-via-tlr7-myd88-dependent-mechanisms
#8
Yan Feng, Lin Zou, Dan Yan, Hongliang Chen, Ganqiong Xu, Wenling Jian, Ping Cui, Wei Chao
Tissue ischemia, such as transient myocardial ischemia, leads to release of cellular RNA including microRNA(miRNA) into the circulation and extracellular (ex-) space, but the biological function of the ex-RNA is poorly understood. We recently reported that cardiac RNA of both human and rodent origins induced cytokine production and immune cell activation. However, the identity of the ex-RNA responsible for the proinflammatory effect remains unclear. In the current study, using an miRNA array, we profiled the plasma miRNAs 4 h after transient myocardial ischemia (45 min) or sham procedure...
August 2, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28761880/therapeutic-effects-of-methanol-extract-from-euphorbia-kansui-radix-on-imiquimod-induced-psoriasis
#9
Soo Jeong Kim, Ye Won Jang, Kyung Eun Hyung, Da Kyoung Lee, Kee Hyeob Hyun, So-Young Park, Eon-Sub Park, Kwang Woo Hwang
The roots of Euphorbia kansui, which belong to the family Euphorbiaceae, have been used as a traditional medicine for the treatment of various diseases such as diabetes, ascites, and leukemia. Recently, it was reported that the methylene chloride fraction of E. kansui radix (EKC) regulated the differentiation of Th17 cells and alleviated the symptoms of Th17-related inflammatory bowel disease. Imiquimod (IMQ), a TLR7/8 agonist, has been used to induce psoriasis in a mouse model. In this study, we evaluated the effect of EKC in an IMQ-induced psoriasis model...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28758266/a-ph-sensitive-macromolecular-prodrug-as-tlr7-8-targeting-immune-response-modifier
#10
Stefan Aichhorn, Anne Linhardt, Angela Halfmann, Markus Nadlinger, Stefanie Kirchberger, Manuela Stadler, Barbara Dillinger, Martin Distel, Alexander Dohnal, Ian Teasdale, Wolfgang Schoefberger
The chemical synthesis and biological activity of novel functionalized imidazoquinoline derivatives to generate Toll-like receptor 7/8 specific prodrugs are presented. In vivo activity of ImQs to induce inflammation was confirmed in zebrafish larvae. After covalent ligation to fully biodegradable polyphosphazenes, the macromolecular prodrugs were designed to undergo intracellular pH-sensitive release of ImQs to induce inflammation through binding to endosomal TLR7/8. We showed ImQ dissociation from prodrugs at a pH 5 pointing towards endosomal prodrug degradability...
July 30, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28754746/tumor-derived-exosomes-modulate-pd-l1-expression-in-monocytes
#11
Franziska Haderk, Ralph Schulz, Murat Iskar, Laura Llaó Cid, Thomas Worst, Karolin V Willmund, Angela Schulz, Uwe Warnken, Jana Seiler, Axel Benner, Michelle Nessling, Thorsten Zenz, Maria Göbel, Jan Dürig, Sven Diederichs, Jérôme Paggetti, Etienne Moussay, Stephan Stilgenbauer, Marc Zapatka, Peter Lichter, Martina Seiffert
In chronic lymphocytic leukemia (CLL), monocytes and macrophages are skewed toward protumorigenic phenotypes, including the release of tumor-supportive cytokines and the expression of immunosuppressive molecules such as programmed cell death 1 ligand 1 (PD-L1). To understand the mechanism driving protumorigenic skewing in CLL, we evaluated the role of tumor cell-derived exosomes in the cross-talk with monocytes. We carried out RNA sequencing and proteome analyses of CLL-derived exosomes and identified noncoding Y RNA hY4 as a highly abundant RNA species that is enriched in exosomes from plasma of CLL patients compared with healthy donor samples...
July 28, 2017: Science Immunology
https://www.readbyqxmd.com/read/28752959/genetic-variations-in-toll-like-receptors-7-and-8-modulate-natural-hepatitis-c-outcomes-and-liver-disease-progression
#12
Fatima-Zohra Fakhir, Mustapha Lkhider, Wafaa Badre, Rhimou Alaoui, Eliane F Meurs, Pascal Pineau, Sayeh Ezzikouri, Soumaya Benjelloun
BACKGROUND & AIMS: The natural outcomes of hepatitis C virus (HCV) as well as the progression of the liver disease are highly variable and depend primarily on an efficient immune response. As Toll-like receptors 7 (TLR7) and 8 (TLR8) are important effectors of the innate immunity, the present study aims to evaluate the association between TLR7 and TLR8 polymorphisms and the HCV infection outcomes in Moroccan subjects. METHODS: In this case-control study, 643 subjects including 293 mild chronic hepatitis patients, 119 with advanced liver disease (AdLD), 93 with HCV spontaneous clearance and 138 healthy controls were genotyped using TaqMan SNPs assays...
July 28, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28751890/tlr7-tlr9-and-b-cell-receptor-signaling-crosstalk-promotion-of-potentially-dangerous-b-cells
#13
REVIEW
Amy N Suthers, Stefanie Sarantopoulos
B cells are capable of receptor-mediated responses to foreign antigens. Recognition of microbial-derived nucleic acid (NA) by toll-like receptors (TLRs) 7 and 9 in B cells has been substantiated. Endogenous NA released from damaged or dying cells can also be immunogenic in certain contexts and can incite aberrant activation of B cells. When TLR-driven B cell receptor (BCR)-activated B cells are not properly constrained, pathologic autoantibodies are produced. It is also clear that endosomal TLR7/TLR9 can operate in conjunction with BCR...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28751765/a-tlr7-agonist-enhances-the-antitumor-efficacy-of-obinutuzumab-in-murine-lymphoma-models-via-nk-cells-and-cd4-t-cells
#14
E J Cheadle, G Lipowska-Bhalla, S J Dovedi, E Fagnano, C Klein, J Honeychurch, T M Illidge
This corrects the article DOI: 10.1038/leu.2016.352.
July 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28744288/naltrexone-inhibits-il-6-and-tnf%C3%AE-production-in-human-immune-cell-subsets-following-stimulation-with-ligands-for-intracellular-toll-like-receptors
#15
Rachel Cant, Angus G Dalgleish, Rachel L Allen
The opioid antagonist naltrexone hydrochloride has been suggested to be a potential therapy at low dosage for multiple inflammatory conditions and cancers. Little is known about the immune-modulating effects of naltrexone, but an effect on the activity of toll-like receptor 4 (TLR4) has been reported. We analyzed the effects of naltrexone hydrochloride on IL-6 secretion by peripheral blood mononuclear cells (PBMC) in vitro following stimulation with ligands for TLR4 and for the intracellular receptors TLR7, TLR8, and TLR9...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28724768/synthetic-tlr4-and-tlr7-ligands-work-additively-via-myd88-to-induce-protective-antiviral-immunity-in-mice
#16
Peter H Goff, Tomoko Hayashi, Wenqian He, Shiyin Yao, Howard B Cottam, Gene S Tan, Brian Crain, Florian Krammer, Karen Messer, Minya Pu, Dennis A Carson, Peter Palese, Maripat Corr
We have previously demonstrated that the combination of synthetic small molecule Toll-like receptor 4 (TLR4) and TLR7 ligands is a potent adjuvant for recombinant influenza virus hemagglutinin, inducing rapid and sustained immunity protective against influenza viruses in homologous, heterologous and heterosubtypic murine challenge models. Combining TLR4 and TLR7 ligands balances Th1/Th2-type immune responses for long-lived cellular and neutralizing humoral immunity against the viral hemagglutinin. Here, we demonstrate that the protective response induced in mice by this combined adjuvant is dependent upon TLR4 and TLR7 signaling via myeloid differentiation primary response gene 88 (MyD88), indicating that the adjuvants function in vivo via their known receptors with negligible off-target effects to induce protective immunity...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28720097/a-versatile-papaya-mosaic-virus-papmv-vaccine-platform-based-on-sortase-mediated-antigen-coupling
#17
Ariane Thérien, Mikaël Bédard, Damien Carignan, Gervais Rioux, Louis Gauthier-Landry, Marie-Ève Laliberté-Gagné, Marilène Bolduc, Pierre Savard, Denis Leclerc
BACKGROUND: Flexuous rod-shaped nanoparticles made of the coat protein (CP) of papaya mosaic virus (PapMV) have been shown to trigger innate immunity through engagement of toll-like receptor 7 (TLR7). PapMV nanoparticles can also serve as a vaccine platform as they can increase the immune response to fused peptide antigens. Although this approach shows great potential, fusion of antigens directly to the CP open reading frame (ORF) is challenging because the fused peptides can alter the structure of the CP and its capacity to self assemble into nanoparticles-a property essential for triggering an efficient immune response to the peptide...
July 18, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28715461/tlr1-10-nf-%C3%AE%C2%BAb-and-p53-expression-is-increased-in-oral-lichenoid-disease
#18
Peter Rusanen, Emilia Marttila, Johanna Uittamo, Jaana Hagström, Tuula Salo, Riina Rautemaa-Richardson
Toll-like receptors (TLRs) and nuclear factor-κB (NF-κB) in keratinocytes play an important role in dermatological autoimmune diseases. Tumour suppressor protein p53 regulates TLR expression. The aim of this study was to compare the expression of TLR1-TLR10, p53 and NF-κB in patients with oral lichenoid disease (OLD) with healthy mucosa. Oral mucosal biopsies from 24 patients with OLD and 26 healthy controls (HC) were analysed for the expression of TLR1-TLR10, NF-κB and p53 by immunohistochemistry. The expression of all TLRs was increased in OLD epithelia compared to HC samples and the difference was significant in TLR1, TLR3, TLR4, TLR5, TLR6 and TLR7...
2017: PloS One
https://www.readbyqxmd.com/read/28712404/-polymorphisms-of-tlr7-rs3853839-and-rs179010-are-associated-with-susceptibility-to-and-severity-of-hand-foot-and-mouth-disease-caused-by-enterovirus-71-in-male-children
#19
Yaping Li, Song Zhai, Mei Li, Yuan Wang, Tong Lu, Huiling Deng, Xin Zhang, Shuangsuo Dang
Objective To investigate whether the polymorphisms of TLR7/MyD88 signaling pathway is associated with the susceptibility to and severity of hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) in children. Methods We collected 180 EV71 HFMD cases and 201 healthy controls from both the Second Affiliated Hospital of Xi'an Jiaotong University and Xi'an Children's Hospital. The genotypes including rs3853839, rs179010 of TLR7, and rs7744 of MyD88 were detected in the 381 samples by SNPscan kit. Results The susceptibility risk (OR=2...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28707750/arterial-immune-protein-expression-demonstrates-the-complexity-of-immune-responses-in-kawasaki-disease-arteritis
#20
S A Cameron, S M White, D Arrollo, S T Shulman, A H Rowley
A more complete understanding of immune-mediated damage to the coronary arteries in children with Kawasaki disease (KD) is required for improvements in patient treatment and outcomes. We recently reported the transcriptional profile of KD coronary arteritis, and in this study sought to determine protein expression of transcriptionally up-regulated immune genes in KD coronary arteries from the first 2 months after disease onset. We examined the coronary arteries of 12 fatal KD cases and 13 childhood controls for expression of a set of proteins whose genes were highly up-regulated in the KD coronary artery transcriptome: allograft inflammatory factor 1 (AIF1), interleukin 18 (IL-18), CD74, CD1c, CD20 (MS4A1), Toll-like receptor 7 (TLR-7) and Z-DNA binding protein 1 (ZBP1)...
July 14, 2017: Clinical and Experimental Immunology
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