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https://www.readbyqxmd.com/read/28900156/dual-roles-of-two-isoforms-of-autophagy-related-gene-atg10-in-hcv-subgenomic-replicon-mediated-autophagy-flux-and-innate-immunity
#1
Qiong Zhao, Zhan-Ying Hu, Jing-Pu Zhang, Jian-Dong Jiang, Yuan-Yuan Ma, Jian-Rui Li, Zong-Gen Peng, Jin-Hua Chen
Autophagy and immune response are two defense systems that human-body uses against viral infection. Previous studies documented that some viral mechanisms circumvented host immunity mechanisms and hijacked autophagy for its replication and survival. Here, we focus on interactions between autophagy mechanism and innate-immune-response in HCV-subgenomic replicon cells to find a mechanism linking the two pathways. We report distinct effects of two autophagy-related protein ATG10s on HCV-subgenomic replication...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28892752/graphene-quantum-dots-suppress-proinflammatory-t-cell-responses-via-autophagy-dependent-induction-of-tolerogenic-dendritic-cells
#2
Sergej Tomić, Kristina Janjetović, Dušan Mihajlović, Marina Milenković, Tamara Kravić-Stevović, Zoran Marković, Biljana Todorović-Marković, Zdenko Spitalsky, Matej Micusik, Dragana Vučević, Miodrag Čolić, Vladimir Trajković
Graphene quantum dots (GQD) are atom-thick nanodimensional carbon sheets with excellent physico-chemical and biological properties, making them attractive for application in theranostics. However, their immunoregulatory properties are insufficiently investigated, especially in human primary immune cells. We found that non-toxic doses of GQD inhibit the production of proinflammatory and T helper (Th)1 cytokines, and augment the production of anti-inflammatory and Th2 cytokines by human peripheral blood mononuclear cells...
August 29, 2017: Biomaterials
https://www.readbyqxmd.com/read/28889952/ormdl3-upregulates-airway-smooth-muscle-proliferation-contraction-and-ca-2-oscillations-in-asthma
#3
Jun Chen, Marina Miller, Hirotoshi Unno, Peter Rosenthal, Michael Sanderson, David H Broide
BACKGROUND: Airway hyperresponsiveness (AHR) is a major feature of asthma attributed predominantly to an extrinsic immune/inflammatory response increasing airway smooth muscle (ASM) contractility. OBJECTIVE: We investigated whether increased ASM expression of ORMDL3, a gene on chromosome 17q21 highly linked to asthma, induced increased ASM proliferation and contractility in vitro, as well as influenced airway contractility and calcium flux in ASM in precision cut lung slices from WT and hORMDL3(Zp3-Cre) mice (which express increased levels of human ORMDL3)...
September 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28871219/p2x7-receptor-activation-modulates-autophagy-in-sod1-g93a-mouse-microglia
#4
Paola Fabbrizio, Susanna Amadio, Savina Apolloni, Cinzia Volonté
Autophagy and inflammation play determinant roles in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), an adult-onset neurodegenerative disease characterized by deterioration and final loss of upper and lower motor neurons (MN) priming microglia to sustain neuroinflammation and a vicious cycle of neurodegeneration. Given that extracellular ATP through P2X7 receptor constitutes a neuron-to-microglia alarm signal implicated in ALS, and that P2X7 affects autophagy in immune cells, we have investigated if autophagy can be directly triggered by P2X7 activation in primary microglia from superoxide dismutase 1 (SOD1)-G93A mice...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28869687/ancestral-acquisitions-gene-flow-and-multiple-evolutionary-trajectories-of-the-type-three-secretion-system-and-effectors-in-xanthomonas-plant-pathogens
#5
Déborah Merda, Martial Briand, Eran Bosis, Céline Rousseau, Perrine Portier, Matthieu Barret, Marie-Agnès Jacques, Marion Fischer-Le Saux
Deciphering the evolutionary history and transmission patterns of virulence determinants is necessary to understand the emergence of novel pathogens. The main virulence determinant of most pathogenic proteobacteria is the type three secretion system (T3SS). The Xanthomonas genus includes bacteria responsible for numerous epidemics in agroecosystems worldwide and represents a major threat to plant health. The main virulence factor of Xanthomonas is the Hrp2 family T3SS, however this system is not conserved in all strains and it has not been previously determined whether the distribution of T3SS in this bacterial genus has resulted from losses or independent acquisitions...
September 4, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28867169/nitric-oxide-the-forgotten-child-of-tumor-metabolism
#6
REVIEW
Bahar Salimian Rizi, Abhinav Achreja, Deepak Nagrath
Nitric oxide (NO) is a signaling molecule with pleiotropic physiological roles in normal cells and pathophysiological roles in cancer. NO synthetase expression and NO synthesis are linked to altered metabolism, neoplasticity, invasiveness, chemoresistance, immune evasion, and ultimately to poor prognosis of cancer patients. Exogenous NO in the microenvironment facilitates paracrine signaling, mediates immune responses, and triggers angiogenesis. NO regulates posttranslational protein modifications, S-nitrosation, and genome-wide epigenetic modifications that can have both tumor-promoting and tumor-suppressing effects...
September 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28855873/molecular-characterization-of-barrier-properties-in-follicle-associated-epithelium-of-porcine-peyer-s-patches-reveals-major-sealing-function-of-claudin-4
#7
Judith Radloff, Evgeny L Falchuk, Alexander G Markov, Salah Amasheh
The pig represents a preferred model for the analysis of intestinal immunology. However, the barrier of the follicle-associated epithelium (FAE) covering porcine Peyer's patches (PP) has not yet been characterized in detail. This study aimed to perform this characterization in order to pave the way toward an understanding of the functional contribution of epithelial barrier properties in gut immunology. Porcine tissue specimens were taken from the distal small intestine in order to obtain electrophysiological data of PP FAE and neighboring villous epithelium (VE), employing the Ussing chamber technique...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28852166/a-dynamic-metabolic-flux-analysis-of-myeloid-derived-suppressor-cells-confirms-immunosuppression-related-metabolic-plasticity
#8
Guillaume Goffaux, Iness Hammami, Mario Jolicoeur
Recent years have witnessed an increasing interest at understanding the role of myeloid-derived suppressor cells (MDSCs) in cancer-induced immunosuppression, with efforts to inhibit their maturation and/or their activity. We have thus modelled MDSCs central carbon metabolism and bioenergetics dynamic, calibrating the model using experimental data on in vitro matured mice bone marrow cells into MDSCs. The model was then used to probe the cells metabolic state and dynamics, performing a dynamic metabolic flux analysis (dMFA) study...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28845460/integration-of-metabolomics-and-transcriptomics-reveals-a-complex-diet-of-mycobacterium-tuberculosis-during-early-macrophage-infection
#9
Michael Zimmermann, Maria Kogadeeva, Martin Gengenbacher, Gayle McEwen, Hans-Joachim Mollenkopf, Nicola Zamboni, Stefan Hugo Ernst Kaufmann, Uwe Sauer
Nutrient acquisition from the host environment is crucial for the survival of intracellular pathogens, but conceptual and technical challenges limit our knowledge of pathogen diets. To overcome some of these technical roadblocks, we exploited an experimentally accessible model for early infection of human macrophages by Mycobacterium tuberculosis, the etiological agent of tuberculosis, to study host-pathogen interactions with a multi-omics approach. We collected metabolomics and complete transcriptome RNA sequencing (dual RNA-seq) data of the infected macrophages, integrated them in a genome-wide reaction pair network, and identified metabolic subnetworks in host cells and M...
July 2017: MSystems
https://www.readbyqxmd.com/read/28841718/inverted-recruitment-of-autophagy-proteins-to-the-plasmodium-berghei-parasitophorous-vacuole-membrane
#10
Jacqueline Schmuckli-Maurer, Vera Reber, Rahel Wacker, Annina Bindschedler, Anthony Zakher, Volker Theo Heussler
Selective autophagy and related mechanisms can act as variable defense mechanisms against pathogens and can therefore be considered as intracellular immune responses. When in hepatocytes, Plasmodium parasites reside in a parasitophorous vacuole (PV) and the PV membrane (PVM) is the main contact site between host cell and parasite. Early in infection, the PVM is directly labeled with host cell autophagy proteins LC3B and p62 (nucleoporin 62). We investigated the recruitment of different selective autophagy receptors and could show that mainly p62 and NBR1 (neighbour of BRCA1 gene 1) and to a lesser extent NDP52 (nuclear dot protein 52) associate with the PVM...
2017: PloS One
https://www.readbyqxmd.com/read/28831154/lineage-structure-of-streptococcus-pneumoniae-may-be-driven-by-immune-selection-on-the-groel-heat-shock-protein
#11
José Lourenço, Eleanor R Watkins, Uri Obolski, Samuel J Peacock, Callum Morris, Martin C J Maiden, Sunetra Gupta
Populations of Streptococcus pneumoniae (SP) are typically structured into groups of closely related organisms or lineages, but it is not clear whether they are maintained by selection or neutral processes. Here, we attempt to address this question by applying a machine learning technique to SP whole genomes. Our results indicate that lineages evolved through immune selection on the groEL chaperone protein. The groEL protein is part of the groESL operon and enables a large range of proteins to fold correctly within the physical environment of the nasopharynx, thereby explaining why lineage structure is so stable within SP despite high levels of genetic transfer...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28812547/lung-epithelial-cells-therapeutically-inducible-effectors-of-antimicrobial-defense
#12
REVIEW
M M Leiva-Juárez, J K Kolls, S E Evans
Lung epithelial cells are increasingly recognized to be active effectors of microbial defense, contributing to both innate and adaptive immune function in the lower respiratory tract. As immune sentinels, lung epithelial cells detect diverse pathogens through an ample repertoire of membrane-bound, endosomal, and cytosolic pattern-recognition receptors (PRRs). The highly plastic epithelial barrier responds to detected threats via modulation of paracellular flux, intercellular communications, mucin production, and periciliary fluid composition...
August 16, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28811364/mechanosensing-drives-acuity-of-%C3%AE-%C3%AE-t-cell-recognition
#13
Yinnian Feng, Kristine N Brazin, Eiji Kobayashi, Robert J Mallis, Ellis L Reinherz, Matthew J Lang
T lymphocytes use surface [Formula: see text] T-cell receptors (TCRs) to recognize peptides bound to MHC molecules (pMHCs) on antigen-presenting cells (APCs). How the exquisite specificity of high-avidity T cells is achieved is unknown but essential, given the paucity of foreign pMHC ligands relative to the ubiquitous self-pMHC array on an APC. Using optical traps, we determine physicochemical triggering thresholds based on load and force direction. Strikingly, chemical thresholds in the absence of external load require orders of magnitude higher pMHC numbers than observed physiologically...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28805674/hepatitis-c-virus-induced-autophagy-and-host-innate-immune-response
#14
REVIEW
Stephanie T Chan, Jing-Hsiung James Ou
Autophagy is a catabolic process that is important for maintaining cellular homeostasis. This pathway in hepatocytes is stimulated and controlled by the hepatitis C virus (HCV)-upon infection-to promote its own replication. HCV induces autophagy indirectly and directly through different mechanisms and temporally controls the autophagic flux. This enables the virus to maximize its replication and attenuate the innate immune responses that it activates. In this review, we discuss the relationship between HCV and autophagy, and the crosstalk between HCV-induced autophagy and host innate immune responses...
August 12, 2017: Viruses
https://www.readbyqxmd.com/read/28805660/prolyl-hydroxylase-2-inactivation-enhances-glycogen-storage-and-promotes-excessive-neutrophilic-responses
#15
Pranvera Sadiku, Joseph A Willson, Rebecca S Dickinson, Fiona Murphy, Alison J Harris, Amy Lewis, David Sammut, Ananda S Mirchandani, Eilise Ryan, Emily R Watts, A A Roger Thompson, Helen M Marriott, David H Dockrell, Cormac T Taylor, Martin Schneider, Patrick H Maxwell, Edwin R Chilvers, Massimilliano Mazzone, Veronica Moral, Chris W Pugh, Peter J Ratcliffe, Christopher J Schofield, Bart Ghesquiere, Peter Carmeliet, Moira Kb Whyte, Sarah R Walmsley
Fully activated innate immune cells are required for effective responses to infection, but their prompt deactivation and removal are essential for limiting tissue damage. Here, we have identified a critical role for the prolyl hydroxylase enzyme Phd2 in maintaining the balance between appropriate, predominantly neutrophil-mediated pathogen clearance and resolution of the innate immune response. We demonstrate that myeloid-specific loss of Phd2 resulted in an exaggerated inflammatory response to Streptococcus pneumonia, with increases in neutrophil motility, functional capacity, and survival...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28801560/imaging-active-infection-in-vivo-using-d-amino-acid-derived-pet-radiotracers
#16
Kiel D Neumann, Javier E Villanueva-Meyer, Christopher A Mutch, Robert R Flavell, Joseph E Blecha, Tiffany Kwak, Renuka Sriram, Henry F VanBrocklin, Oren S Rosenberg, Michael A Ohliger, David M Wilson
Occult bacterial infections represent a worldwide health problem. Differentiating active bacterial infection from sterile inflammation can be difficult using current imaging tools. Present clinically viable methodologies either detect morphologic changes (CT/ MR), recruitment of immune cells ((111)In-WBC SPECT), or enhanced glycolytic flux seen in inflammatory cells ((18)F-FDG PET). However, these strategies are often inadequate to detect bacterial infection and are not specific for living bacteria. Recent approaches have taken advantage of key metabolic differences between prokaryotic and eukaryotic organisms, allowing easier distinction between bacteria and their host...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28798231/p2x7-receptor-antagonism-prevents-il-1%C3%AE-release-from-salivary-epithelial-cells-and-reduces-inflammation-in-a-mouse-model-of-autoimmune-exocrinopathy
#17
Mahmoud G Khalafalla, Lucas T Woods, Jean M Camden, Aslam A Khan, Kirsten H Limesand, Michael J Petris, Laurie Erb, Gary A Weisman
Salivary gland inflammation is a hallmark of Sjogrens syndrome (SS), a common autoimmune disease characterized by lymphocytic infiltration of the salivary gland and loss of saliva secretion, predominantly in women. The P2X7 receptor (P2X7R) is an ATP-gated non-selective cation channel that induces inflammatory responses in cells and tissues, including salivary gland epithelium. In immune cells, P2X7R activation induces the production of proinflammatory cytokines, including IL-1β and IL-18, by inducing the oligomerization of the multiprotein complex NLRP3-type inflammasome...
August 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28796780/transcriptome-and-proteome-analysis-of-salmonella-enterica-serovar-typhimurium-systemic-infection-of-wild-type-and-immune-deficient-mice
#18
Olusegun Oshota, Max Conway, Maria Fookes, Fernanda Schreiber, Roy R Chaudhuri, Lu Yu, Fiona J E Morgan, Simon Clare, Jyoti Choudhary, Nicholas R Thomson, Pietro Lio, Duncan J Maskell, Pietro Mastroeni, Andrew J Grant
Salmonella enterica are a threat to public health. Current vaccines are not fully effective. The ability to grow in infected tissues within phagocytes is required for S. enterica virulence in systemic disease. As the infection progresses the bacteria are exposed to a complex host immune response. Consequently, in order to continue growing in the tissues, S. enterica requires the coordinated regulation of fitness genes. Bacterial gene regulation has so far been investigated largely using exposure to artificial environmental conditions or to in vitro cultured cells, and little information is available on how S...
2017: PloS One
https://www.readbyqxmd.com/read/28780484/expression-of-hepcidin-and-ferroportin-in-full-term-placenta-of-pregnant-cows
#19
Sante Roperto, Valeria Russo, Chiara Urraro, Anna Cutarelli, Antonella Perillo, Francesca De Falco, Franco Roperto
Hepcidin (HEP) and ferroportin (FPN) play a central role in systemic iron homeostasis. The HEP/FPN axis controls both extracellular iron concentration and total body iron levels. HEP is synthesized mainly by hepatocytes and controls the absorption of dietary iron and the distribution of iron to the various cell types; its synthesis is regulated by both iron and innate immunity. FPN is a membrane protein and the major exporter of iron from mammalian cells, including iron recycling macrophages, iron absorbing duodenal enterocytes, and iron storing hepatocytes...
November 2017: Theriogenology
https://www.readbyqxmd.com/read/28768817/cxcr4-specific-nanobodies-as-potential-therapeutics-for-whim-syndrome
#20
Raymond H de Wit, Raimond Heukers, Hendrik Brink, Angela Arsova, David Maussang, Pasquale Cutolo, Beatrijs Strubbe, Henry Vischer, Francoise Bachelerie, Martine J Smit
WHIM syndrome is a rare congenital immunodeficiency disease, named after its main clinical manifestations: Warts, Hypogammaglobulinemia, Infections and Myelokathexis. The disease is primarily caused by C-terminal truncation mutations of the chemokine receptor CXCR4. Consequently, these CXCR4-WHIM mutants have a gain of function in response to its ligand CXCL12, which results in abnormal leukocyte migration and thereby immune system dysfunctions. Treatment of WHIM patients currently consists of symptom relief, leading to unsatisfactory clinical responses...
August 2, 2017: Journal of Pharmacology and Experimental Therapeutics
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