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https://www.readbyqxmd.com/read/28812547/lung-epithelial-cells-therapeutically-inducible-effectors-of-antimicrobial-defense
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
July 27, 2017: Theriogenology
https://www.readbyqxmd.com/read/28768817/cxcr4-specific-nanobodies-as-potential-therapeutics-for-whim-syndrome
#9
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
https://www.readbyqxmd.com/read/28766554/campylobacter-jejuni-impairs-sodium-transport-and-epithelial-barrier-function-via-cytokine-release-in-human-colon
#10
R Bücker, S M Krug, V Moos, C Bojarski, M R Schweiger, M Kerick, A Fromm, S Janßen, M Fromm, N A Hering, B Siegmund, T Schneider, C Barmeyer, J D Schulzke
Campylobacter jejuni is the most prevalent cause of foodborne bacterial enteritis worldwide. Patients present with diarrhea and immune responses lead to complications like arthritis and irritable bowel syndrome. Although studies exist in animal and cell models, we aimed at a functional and structural characterization of intestinal dysfunction and the involved regulatory mechanisms in human colon. First, in patients' colonic biopsies, sodium malabsorption was identified as an important diarrheal mechanism resulting from hampered epithelial ion transport via impaired epithelial sodium channel (ENaC) β- and γ-subunit...
August 2, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28760569/jasmonic-acid-oxidase-2-jao2-hydroxylates-jasmonic-acid-and-represses-basal-defense-and-resistance-responses-against-botrytis-cinerea-infection
#11
Ekaterina Smirnova, Valentin Marquis, Laure Poirier, Yann Aubert, Julie Zumsteg, Rozenn Ménard, Laurence Miesch, Thierry Heitz
Jasmonates (JAs) orchestrate immune responses upon wound/herbivore injury or infection by necrotrophic pathogens. Elucidation of catabolic routes has revealed new complexity in jasmonate metabolism. Two integrated pathways attenuate signaling by turning over the active hormone jasmonoyl-isoleucine (JA-Ile) through ω-oxidation or deconjugation, and define an indirect route forming the derivative 12OH-JA. Here we provide evidence for a second 12OH-JA formation pathway by direct jasmonic acid (JA) oxidation. Three Jasmonic Acid Oxidases (JAO) of the 2-oxoglutarate dioxygenase family catalyze specific oxidation of JA to 12OH-JA and their genes are induced by wounding or infection by the fungus Botrytis cinerea...
July 28, 2017: Molecular Plant
https://www.readbyqxmd.com/read/28743432/high-levels-of-eukaryotic-initiation-factor-6-eif6-are-required-for-immune-system-homeostasis-and-for-steering-the-glycolytic-flux-of-tcr-stimulated-cd4-t-cells-in-both-mice-and-humans
#12
Nicola Manfrini, Sara Ricciardi, Annarita Miluzio, Maya Fedeli, Alessandra Scagliola, Simone Gallo, Daniela Brina, Thure Adler, Dirk H Busch, Valerie Gailus-Durner, Helmut Fuchs, Martin Hrabě de Angelis, Stefano Biffo
Eukaryotic Initiation Factor 6 (eIF6) is required for 60S ribosomal subunit biogenesis and efficient initiation of translation. Intriguingly, in both mice and humans, endogenous levels of eIF6 are detrimental as they act as tumor and obesity facilitators, raising the question on the evolutionary pressure that maintains high eIF6 levels. Here we show that, in mice and humans, high levels of eIF6 are required for proper immune functions. First, eIF6 heterozygous (het) mice show an increased mortality during viral infection and a reduction of peripheral blood CD4(+) Effector Memory T cells...
July 22, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28708972/uv-irradiation-of-skin-enhances-glycolytic-flux-and-reduces-migration-capabilities-in-bone-marrow-differentiated-dendritic-cells
#13
Terence A McGonigle, Kevin N Keane, Simon Ghaly, Kim W Carter, Denise Anderson, Naomi M Scott, Helen S Goodridge, Amy Dwyer, Eloise Greenland, Fiona J Pixley, Philip Newsholme, Prue H Hart
A systemic immunosuppression follows UV irradiation of the skin of humans and mice. In this study, dendritic cells (DCs) differentiating from the bone marrow of UV-irradiated mice had a reduced ability to migrate toward the chemokine (C-C motif) ligand 21. Fewer DCs also accumulated in the peritoneal cavity of UV-chimeric mice (ie, mice transplanted with bone marrow from UV-irradiated mice) after injection of an inflammatory stimulus into that site. We hypothesized that different metabolic states underpin altered DC motility...
July 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28705991/oxygen-metabolism-and-innate-immune-responses-in-the-gut
#14
Sean Patrick Colgan, Eric L Campbell
Epithelial cells of the mucosa provide a first line of protection against the inappropriate flux of antigens from the outside world. In the gastrointestinal (GI) tract, this barrier is provided at a number of levels, including mucus production, epithelial junctional complexes and the production of antimicrobial molecules. In recent years, it is better appreciated that tissue oxygen metabolism is key to homeostasis in the mucosa. The intestine, for example, maintains a low baseline pO2 levels due to counter-current blood flow and the presence of large numbers of bacteria...
July 13, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28702931/autophagy-induced-by-bovine-viral-diarrhea-virus-infection-counteracts-apoptosis-and-innate-immune-activation
#15
Yulong Zhou, Yachao Ren, Yanlong Cong, Yu Mu, Renfu Yin, Zhuang Ding
Bovine viral diarrhea virus (BVDV) is an important pathogen of cattle that plays a complex role in disease. There are two biotypes of BVDV: non-cytopathic (NCP) and cytopathic (CP). One strategy that has been used to treat or prevent virus-associated diseases is the modulation of autophagy, which is used by the innate immune system to defend against viral infection; however, at present, the interplay between autophagy and BVDV remains unclear. Madin-Darby bovine kidney cells stably expressing microtubule-associated protein 1 light chain 3B (LC3B) with green fluorescent protein (GFP) (GFP-LC3-MDBK cells) and autophagy-deficient MDBKs (shBCN1-MDBK cells) were constructed...
July 12, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28691995/the-role-of-psychological-stress-on-heart-autophagy-in-mice-with-heart-failure
#16
Xiao-Ting Lu, Xiao-Qiong Liu, Bo Wang, Yuan-Yuan Sun, Rui-Xue Yang, Yi-Fan Xing, Ping Sun, Ying-Bin Wang, Yu-Xia Zhao
OBJECTIVE: Psychological stress in chronic heart failure (CHF) is associated with systemic neurohormonal and immune system responses and increased mortality. Autophagy refers to the biological process of degradation and recycling of dysfunctional cellular components. We investigated the role of psychological stress on autophagy function in CHF mice. RESULTS: A one-week stress exposure significantly increased serum levels of corticosterone and Ang II (P= .000), increased levels of oxidative stress, induced overt heart failure, and increased mortality (P =...
July 7, 2017: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28690610/toll-like-receptor-4-inhibition-improves-oxidative-stress-and-mitochondrial-health-in-isoproterenol-induced-cardiac-hypertrophy-in-rats
#17
Parmeshwar B Katare, Pankaj K Bagul, Amit K Dinda, Sanjay K Banerjee
BACKGROUND: Inflammation remains a crucial factor for progression of cardiac diseases and cardiac hypertrophy remains an important cause of cardiac failure over all age groups. As a key regulator of inflammation, toll-like receptor 4 (TLR4) plays an important role in pathogenesis of cardiac diseases. Being an important regulator of innate immunity, the precise pathway of TLR4-mediated cardiac complications is yet to be established. Therefore, the primary objective of the present study was to find the role of TLR4 in cardiac hypertrophy and the molecular mechanism thereof...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28690139/4-aroyl-3-hydroxy-5-phenyl-1h-pyrrol-2-5h-ones-as-n-formyl-peptide-receptor-1-fpr1-antagonists
#18
Liliya N Kirpotina, Igor A Schepetkin, Andrei I Khlebnikov, Olga I Ruban, Yunjun Ge, Richard D Ye, Douglas J Kominsky, Mark T Quinn
Formyl peptide receptors (FPRs) are expressed on a variety of leukocytes and play important roles in inflammation. Thus, FPR antagonists may represent novel therapeutics for modulating innate immunity and treating inflammatory diseases. Previously, 1H-pyrrol-2(5H)-ones were reported to be potent and competitive FPR1 antagonists. In the present studies, 42 additional 1H-pyrrol-2(5H)-one analogs were evaluated for FPR1 antagonist activity. We identified a number of novel competitive FPR1 antagonists that inhibited N-formylmethionyl-leucyl-phenylalanine (fMLF)-induced intracellular Ca(2+) mobilization in FPR1-transfected HL60 cells and effectively competed with WKYMVm-FITC for binding to FPR1 in FPR1-transfected RBL cells...
July 6, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28685841/krebs-cycle-rewired-for-macrophage-and-dendritic-cell-effector-functions
#19
REVIEW
Dylan Gerard Ryan, Luke A J O'Neill
The Krebs cycle is an amphibolic pathway operating in the mitochondrial matrix of all eukaryotic organisms. In response to proinflammatory stimuli, macrophages and dendritic cells undergo profound metabolic remodelling to support the biosynthetic and bioenergetic requirements of the cell. Recently, it has been discovered that this metabolic shift also involves the rewiring of the Krebs cycle to regulate cellular metabolic flux and the accumulation of Krebs cycle intermediates, notably, citrate, succinate and fumarate...
July 7, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28676351/bidirectional-brain-gut-interactions-and-chronic-pathological-changes-after-traumatic-brain-injury-in-mice
#20
Elise L Ma, Allen D Smith, Neemesh Desai, Lumei Cheung, Marie Hanscom, Bogdan A Stoica, David J Loane, Terez Shea-Donohue, Alan I Faden
OBJECTIVES: Traumatic brain injury (TBI) has complex effects on the gastrointestinal tract that are associated with TBI-related morbidity and mortality. We examined changes in mucosal barrier properties and enteric glial cell response in the gut after experimental TBI in mice, as well as effects of the enteric pathogen Citrobacter rodentium (Cr) on both gut and brain after injury. METHODS: Moderate-level TBI was induced in C57BL/6 mice by controlled cortical impact (CCI)...
July 1, 2017: Brain, Behavior, and Immunity
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