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https://www.readbyqxmd.com/read/28228559/targeting-influenza-virus-hemagglutinin-to-xcr1-dendritic-cells-in-the-absence-of-receptor-mediated-endocytosis-enhances-protective-antibody-responses
#1
Arnar Gudjonsson, Anna Lysén, Sreekumar Balan, Vibeke Sundvold-Gjerstad, Catharina Arnold-Schrauf, Lisa Richter, Espen S Bækkevold, Marc Dalod, Bjarne Bogen, Even Fossum
Targeting Ags to conventional dendritic cells can enhance Ag-specific immune responses. Although most studies have focused on the induction of T cell responses, the mechanisms by which targeting improves Ab responses are poorly understood. In this study we present data on the use of human XCL1 (hXCL1) and hXCL2 fusion vaccines in a murine model. We show that the human chemokines bound type 1 conventional dendritic cells (cDC1), and that immunization with influenza virus hemagglutinin fused to hXCL1 or hXCL2 induced full protection against influenza challenge...
February 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28223351/in-vivo-and-in-vitro-proteome-analysis-of-hiv-1-infected-human-cd4-t-cells
#2
Johannes Nemeth, Valentina Vongrad, Karin J Metzner, Victoria Strouvelle, Rainer Weber, Patrick Pedrioli, Ruedi Aebersold, Huldrych Guenthard, Ben C Collins
Host directed therapies against HIV-1 are thought to be critical for long term containment of the HIV-1 pandemic but remain elusive. Since HIV-1 infects and manipulates important effectors of both the innate and adaptive immune system, identifying modulations of the host cell systems in humans during HIV-1 infection may be crucial for the development of immune based therapies. Here, we quantified the changes of the proteome in human CD4+ T cells upon HIV-1 infection, both in vitro and in vivo. A SWATH-MS approach was used to measure the proteome of human primary CD4+ T cells infected with HIV-1 in vitro as well as CD4+ T cells from HIV-1 infected patients with paired samples on and off antiretroviral treatment...
February 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28220857/samhd1-enhances-nucleoside-analogue-efficacy-against-hiv-1-in-myeloid-cells
#3
Paula Ordonez, Simone Kunzelmann, Harriet C T Groom, Melvyn W Yap, Simon Weising, Chris Meier, Kate N Bishop, Ian A Taylor, Jonathan P Stoye
SAMHD1 is an intracellular enzyme that specifically degrades deoxynucleoside triphosphates into component nucleoside and inorganic triphosphate. In myeloid-derived dendritic cells and macrophages as well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosphohydrolase activity by reducing the cellular dNTP pool to a level that cannot support productive reverse transcription. We now show that, in addition to this direct effect on virus replication, manipulating cellular SAMHD1 activity can significantly enhance or decrease the anti-HIV-1 efficacy of nucleotide analogue reverse transcription inhibitors presumably as a result of modulating dNTP pools that compete for recruitment by viral polymerases...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28212788/immunology-of-alveolar-and%C3%A2-cystic-echinococcosis-ae-and-ce
#4
B Gottstein, P Soboslay, E Ortona, J Wang, A Siracusano, D Α Vuitton
Cystic and alveolar echinococcosis are severe chronic helminthic diseases caused by the cystic growth or the intrahepatic tumour-like growth of the metacestode of Echinococcus granulosus or Echinococcus multilocularis, respectively. Both parasites have evolved sophisticated strategies to escape host immune responses, mainly by manipulating and directing this immune response towards anergy and/or tolerance. Recent research studies have revealed a number of respective immunoregulatory mechanisms related to macrophages and dendritic cell as well as T cell activities (regulatory T cells, Tregs)...
2017: Advances in Parasitology
https://www.readbyqxmd.com/read/28209611/genetic-manipulation-of-helicobacter-pylori-virulence-function-by-host-carcinogenic-phenotypes
#5
Giovanni Suarez, Judith Romero-Gallo, Johanna C Sierra, M Blanca Piazuelo, Uma Krishna, Martin Alonso Gomez, Keith T Wilson, Richard M Peek
Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma, yet only a minority of infected persons ever develop this malignancy. One cancer-linked locus is the cag type 4 secretion system (cagT4SS), which translocates an oncoprotein into host cells. A structural component of the cagT4SS is CagY, which become rapidly altered during in vivo adaptation in mice and rhesus monkeys, rendering the cagT4SS nonfunctional; however, these models rarely develop gastric cancer. We previously demonstrated that the H...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28205579/tim-3-inhibits-macrophage-control-of-listeria-monocytogenes-by-inhibiting-nrf2
#6
Zhiding Wang, Dejun Sun, Guojiang Chen, Ge Li, Shuaijie Dou, Renxi Wang, He Xiao, Chunmei Hou, Yan Li, Jiannan Feng, Beifen Shen, Gencheng Han
T cell immunoglobulin mucin-3 (Tim-3) is an immune checkpoint inhibitor and its dysregulation has been related to T cell tolerance and many immune disorders, such as tumors and infection tolerance. However, the physiopathology roles of Tim-3 in innate immunity remain elusive. Here, we demonstrate that Tim-3 inhibits macrophage phagocytosis of L. monocytogenes by inhibiting the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway and increases bacterial burden. Tim-3 signaling promotes Nrf2 degradation by increasing its ubiquitination and, as a result, decreasing its nuclear translocation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28192089/dynamic-phenylalanine-clamp-interactions-define-single-channel-polypeptide-translocation-through-the-anthrax-toxin-protective-antigen-channel
#7
Koyel Ghosal, Jennifer M Colby, Debasis Das, Stephen T Joy, Paramjit S Arora, Bryan A Krantz
Anthrax toxin is an intracellularly acting toxin where sufficient detail is known about the structure of its channel, allowing for molecular investigations of translocation. The toxin is comprised of three proteins, protective antigen (PA), lethal factor (LF), and edema factor (EF). The toxin's translocon, PA, translocates the large enzymes, LF and EF, across the endosomal membrane into the host cell's cytosol. Polypeptide clamps located throughout the PA channel catalyze the translocation of LF and EF. Here we show that the central peptide clamp, the ϕ clamp, is a dynamic site that governs the overall peptide translocation pathway...
February 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28187984/construction-of-a-viral-t2a-peptide-based-knock-in-mouse-model-for-enhanced-cre-recombinase-activity-and-fluorescent-labeling-of-podocytes
#8
Sybille Koehler, Sebastian Brähler, Fabian Braun, Henning Hagmann, Markus M Rinschen, Martin R Späth, Martin Höhne, F Thomas Wunderlich, Bernhard Schermer, Thomas Benzing, Paul T Brinkkoetter
Podocyte injury is a key event in glomerular disease leading to proteinuria and opening the path toward glomerular scarring. As a consequence, glomerular research strives to discover molecular mechanisms and signaling pathways affecting podocyte health. The hNphs2.Cre mouse model has been a valuable tool to manipulate podocyte-specific genes and to label podocytes for lineage tracing and purification. Here we designed a novel podocyte-specific tricistronic Cre mouse model combining codon improved Cre expression and fluorescent cell labeling with mTomato under the control of the endogenous Nphs2 promoter using viral T2A-peptides...
February 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28184299/the-role-of-cdc1s-in-vivo-cd8-t-cell-priming-through-cross-presentation
#9
REVIEW
Derek Theisen, Kenneth Murphy
The cDC1 subset of classical dendritic cells is specialized for priming CD8 T cell responses through the process of cross-presentation. The molecular mechanisms of cross-presentation remain incompletely understood because of limited biochemical analysis of rare cDC1 cells, difficulty in their genetic manipulation, and reliance on in vitro systems based on monocyte- and bone-marrow-derived dendritic cells. This review will discuss cross-presentation from the perspective of studies with monocyte- or bone-marrow-derived dendritic cells while highlighting the need for future work examining cDC1 cells...
2017: F1000Research
https://www.readbyqxmd.com/read/28184224/cbl-b-deficiency-mediates-resistance-to-programmed-death-ligand-1-programmed-death-1-regulation
#10
Mai Fujiwara, Emily J Anstadt, Robert B Clark
Casitas B-lineage lymphoma-b (Cbl-b) is an E3 ubiquitin ligase that negatively regulates T cell activation. Cbl-b(-/-) T cells are hyper-reactive and co-stimulation independent, and Cbl-b(-/-) mice demonstrate robust T cell and NK cell-mediated antitumor immunity. As a result of these murine studies, Cbl-b is considered a potential target for therapeutic manipulation in human cancer immunotherapy. The PD-L1/PD-1 pathway of immune regulation is presently an important therapeutic focus in tumor immunotherapy, and although Cbl-b(-/-) mice have been shown to be resistant to several immuno-regulatory mechanisms, the sensitivity of Cbl-b(-/-) mice to PD-L1-mediated suppression has not been reported...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28179159/in-vivo-osteogenic-differentiation-of-stem-cells-inside-compartmentalized-capsules-loaded-with-co-cultured-endothelial-cells
#11
Clara R Correia, Tírcia C Santos, Rogério P Pirraco, Mariana T Cerqueira, Alexandra P Marques, Rui L Reis, João F Mano
: Capsules coated with polyelectrolytes and co-encapsulating adipose stem (ASCs) and endothelial (ECs) cells with surface modified microparticles are developed. Microparticles and cells are freely dispersed in a liquified core, responsible to maximize the diffusion of essential molecules and allowing the geometrical freedom for the autonomous three-dimensional (3D) organization of cells. While the membrane wraps all the instructive cargo elements within a single structure, the microparticles provide a solid 3D substrate for the encapsulated cells...
February 4, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28174572/functional-characterization-of-rhoptry-kinome-in-the-virulent-toxoplasma-gondii-rh-strain
#12
Jin-Lei Wang, Ting-Ting Li, Hany M Elsheikha, Kai Chen, Wei-Ning Zhu, Dong-Mei Yue, Xing-Quan Zhu, Si-Yang Huang
Toxoplasma gondii is an obligatory intracellular apicomplexan protozoan which can infect any warm-blooded animal and causes severe diseases in immunocompromised individuals or infants infected in utero. The survival and success of this parasite require that it colonizes the host cell, avoids host immune defenses, replicates within an appropriate niche, and exits the infected host cell to spread to neighboring non-infected cells. All of these processes depend on the parasite ability to synthesis and export secreted proteins...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28170177/pluripotent-nontumorigenic-adipose-tissue-derived-muse-cells-have-immunomodulatory-capacity-mediated-by-transforming-growth-factor-%C3%AE-1
#13
María L Gimeno, Florencia Fuertes, Andres E Barcala Tabarrozzi, Alejandra I Attorressi, Rodolfo Cucchiani, Luis Corrales, Talita C Oliveira, Mari C Sogayar, Leticia Labriola, Ricardo A Dewey, Marcelo J Perone
Adult mesenchymal stromal cell-based interventions have shown promising results in a broad range of diseases. However, their use has faced limited effectiveness owing to the low survival rates and susceptibility to environmental stress on transplantation. We describe the cellular and molecular characteristics of multilineage-differentiating stress-enduring (Muse) cells derived from adipose tissue (AT), a subpopulation of pluripotent stem cells isolated from human lipoaspirates. Muse-AT cells were efficiently obtained using a simple, fast, and affordable procedure, avoiding cell sorting and genetic manipulation methods...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28167629/il-10-plays-opposing-roles-during-staphylococcus-aureus-systemic-and-localized-infections
#14
John M Leech, Keenan A Lacey, Michelle E Mulcahy, Eva Medina, Rachel M McLoughlin
IL-10 is a potent anti-inflammatory mediator that plays a crucial role in limiting host immunopathology during bacterial infections by controlling effector T cell activation. Staphylococcus aureus has previously been shown to manipulate the IL-10 response as a mechanism of immune evasion during chronic systemic and biofilm models of infection. In the present study, we demonstrate divergent roles for IL-10 depending on the site of infection. During acute systemic S. aureus infection, IL-10 plays an important protective role and is required to prevent bacterial dissemination and host morbidity by controlling effector T cells and the associated downstream hyperactivation of inflammatory phagocytes, which are capable of host tissue damage...
February 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28167152/the-prognostic-limitations-of-donor-t-cell-chimerism-after-myeloablative-allogeneic-stem-cell-transplantation-for-acute-myeloid-leukemia-and-myelodysplastic-syndromes
#15
Eric Wong, Kate Mason, Jenny Collins, Barbara Hockridge, Janis Boyd, Alexandra Gorelik, Jeffrey Szer, David S Ritchie
Donor T-cell chimerism is associated with relapse outcomes after allogeneic stem cell transplantation (alloSCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, measures of statistical association do not adequately assess the performance of a prognostic biomarker, which is best characterized by its sensitivity and specificity for the chosen outcome. We analyzed donor T-cell chimerism results at day 100 (D100chim) after myeloablative alloSCT for AML or MDS in 103 patients, and determined its sensitivity and specificity for relapse free survival at 6 months (RFS6) and 12 months (RFS12) post-alloSCT...
February 3, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28164638/immunomagnetic-t-cell-depletion-an-analysis-of-variables-affecting-final-cell-yield
#16
Julian Sevilla, Maria Guillen, Eva Galvez, Eva Merino, Ana Castillo, Marta Prudencio, Marta Gonzalez-Vicent, Manuel Ramirez, Lorea Abad, Luis Madero, Miguel A Diaz-Perez
BACKGROUND: Only little detailed information has been published by a small number of centers on experiences with the technical aspects of "in vitro" large-scale graft manipulation technologies. METHODS: We report our experiences with the graft engineering procedures performed and the results obtained after T cell depletion. We have analyzed data from 212 procedures (108 CD34+ cell selection and 104 CD3+/CD19+ cell depletion). RESULTS: We conclude that the final cell products after selection or depletion were completely different with regard to CD34+ cell purity (95...
July 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28163304/predominant-contribution-of-dgk%C3%AE-over-dgk%C3%AE-in-the-control-of-pkc-pdk-1-regulated-functions-in-t-cells
#17
A Ávila-Flores, J Arranz-Nicolás, E Andrada, D Soutar, I Mérida
Diacylglycerol kinase (DGK)-mediated consumption of the diacylglycerol (DAG) generated in response to antigen recognition is an important mechanism to limit T cell function. Targeting DGK activity presents new opportunities for therapeutic manipulation of the immune response, but assessment of individual DGK functions is complex. T cells express two DGK isoforms, DGKα and DGKζ, and there are no isoform-specific inhibitors. Here we used siRNA-mediated gene silencing in human T cells and DGKα- and DGKζ-deficient mice to define DGK isoform-specific regulation of key signaling pathways during T cell activation...
February 6, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28153703/cross-talk-among-pmca-calcineurin-and-nfat-transcription-factors-in-control-of-calmodulin-gene-expression-in-differentiating-pc12-cells
#18
Tomasz Boczek, Malwina Lisek, Bozena Ferenc, Ludmila Zylinska
Brain aging is characterized by progressive loss of plasma membrane calcium pump (PMCA) and its activator - calmodulin (CaM), but the mechanism of this phenomenon remains unresolved. CaM encoded by three genes Calm1, Calm2, Calm3, works to translate Ca(2+) signal into changes in frequently opposite cellular activities. This unique function allows CaM to affect gene expression via stimulation of calcineurin (CaN) and its downstream target - nuclear factor of activated T-cells (NFAT) and to terminate Ca(2+) signal by stimulation of its extrusion...
January 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28152393/molecular-cloning-characterization-and-expression-analysis-of-tim-3-and-galectin-9-in-the-woodchuck-model
#19
Yanan Liu, Junzhong Wang, Lu Wang, Baoju Wang, Shangqing Yang, Qin Wang, Jinzhuo Luo, Xuemei Feng, Xuecheng Yang, Yinping Lu, Michael Roggendorf, Mengji Lu, Dongliang Yang, Jia Liu
In recent years, a critical role for T cell immunoglobulin mucin domain 3 (Tim-3) and its ligand Galectin-9 (Gal-9) has emerged in infectious disease, autoimmunity and cancer. Manipulating this immune checkpoint may have immunotherapeutic potential and could represent an alternative approach for improving immune responses to viral infections and cancer. The woodchuck (Marmot monax) infected by woodchuck hepatitis virus (WHV) represents an informative animal model to study HBV infection and HCC. In the current study, the cDNA sequences of woodchuck Tim-3 and Gal-9 were cloned, sequenced and characterized...
March 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28137669/effective-gene-delivery-to-trypanosoma-cruzi-epimastigotes-through-nucleofection
#20
Lisandro Pacheco-Lugo, Yirys Díaz-Olmos, José Sáenz-García, Christian Macagnan Probst, Wanderson Duarte DaRocha
New opportunities have raised to study the gene function approaches of Trypanosoma cruzi after its genome sequencing in 2005. Functional genomic approaches in Trypanosoma cruzi are challenging due to the reduced tools available for genetic manipulation, as well as to the reduced efficiency of the transient transfection conducted through conventional methods. The Amaxa nucleofector device was systematically tested in the present study in order to improve the electroporation conditions in the epimastigote forms of T...
January 27, 2017: Parasitology International
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