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Sterile immunity

Bulent Ergin, Michal Heger, Asli Kandil, Cihan Demirci-Tansel, Can Ince
Ischemia/reperfusion (I/R) is one of the main causes of acute kidney injury (AKI), which is characterized by sterile inflammation and oxidative stress. Immune cell activation can provoke overproduction of inflammatory mediators and reactive oxygen species (ROS), leading to perturbation of the microcirculation and tissue oxygenation associated with local and remote tissue injury. This study investigated whether the clinically employed immunosuppressant mycophenolate mofetil (MMF) was able to reduce I/R-induced renal oxygenation defects and oxidative stress by preventing sterile inflammation...
October 25, 2016: Clinical and Experimental Pharmacology & Physiology
Ping Zeng, Lei Hou, Xiuli He, Qiaoyi Ning, Jing Zhou, Wukai Ma
Objective To observe multi-organ damages at different stages in immune-mediated mouse models of Sjogren's syndrome. Methods Eighty C57BL/6J mice were divided randomly into 2 groups, a blank control group and a model group. Sjogren's syndrome was induced in the 40 mice in the latter group by immune injury. Every 10 mice were killed at 4, 6, 8 and 10 weeks. The submandibular gland, thymus, lung, spleen and kidney were isolated under sterile condition. HE staining was used to observe the pathological changes of the organs under a light microscope...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Qian Sun, Patricia Loughran, Richard Shapiro, Indira H Shrivastava, Daniel J Antoine, Tunliang Li, Zhengzheng Yan, Jie Fan, Timothy R Billiar, Melanie J Scott
: Sterile liver inflammation, such as liver ischemia reperfusion, hemorrhagic shock after trauma and drug-induced liver injury is initiated and regulated by endogenous mediators including DNA and reactive oxygen species. Here we identify a novel mechanism for redox-mediated regulation of AIM2-inflammasome activation in hepatocytes after redox stress in mice, which occurs via interaction with cytosolic HMGB1. We show that in liver during hemorrhagic shock in mice, and in hepatocytes after hypoxia with reoxygenation, cytosolic HMGB1 associates with AIM2 and is required for activation of caspase-1 in response to cytosolic DNA...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Daniel Hachim, Samuel T LoPresti, Cecelia C Yates, Bryan N Brown
The present study tests the hypothesis that transient, early-stage shifts in macrophage polarization at the tissue-implant interface from a pro-inflammatory (M1) to an anti-inflammatory/regulatory (M2) phenotype mitigates the host inflammatory reaction against a non-degradable polypropylene mesh material and improves implant integration downstream. To address this hypothesis, a nanometer-thickness coating capable of releasing IL-4 (an M2 polarizing cytokine) from an implant surface at early stages of the host response has been developed...
October 11, 2016: Biomaterials
Myriam Arévalo-Herrera, Juan M Vásquez-Jiménez, Mary Lopez-Perez, Andrés F Vallejo, Andrés B Amado-Garavito, Nora Céspedes, Angélica Castellanos, Karen Molina, Johanna Trejos, José Oñate, Judith E Epstein, Thomas L Richie, Sócrates Herrera
BACKGROUND: Immunizing human volunteers by mosquito bite with radiation-attenuated Plasmodium falciparum sporozoites (RAS) results in high-level protection against infection. Only two volunteers have been similarly immunized with P. vivax (Pv) RAS, and both were protected. A phase 2 controlled clinical trial was conducted to assess the safety and protective efficacy of PvRAS immunization. METHODOLOGY/PRINCIPAL FINDINGS: A randomized, single-blinded trial was conducted...
October 2016: PLoS Neglected Tropical Diseases
Tatjana Taubitz, Laura-Pia Steinbrenner, Alexander V Tschulakow, Antje Biesemeier, Sylvie Julien-Schraermeyer, Ulrich Schraermeyer
PURPOSE: Anti-vascular endothelial growth factor (VEGF) drugs are used to treat neovascular eye diseases. Some of these drugs contain Fc fragments (Fc), but it is unknown how their mode of action is influenced by Fc. Therefore, this study investigated the effects of Fc on rat eyes after intravitreal injection. METHODS: Eighteen Long-Evans rats were intravitreally injected with sterile, biotin-labeled rat Fc (9.1 μg in 5 μl PBS). For control, 5 μl PBS was injected in another nine rats...
October 17, 2016: Graefe's Archive for Clinical and Experimental Ophthalmology
Yanling Wei, Jun Yang, Jun Wang, Yang Yang, Juan Huang, Hao Gong, Hongli Cui, Dongfeng Chen
BACKGROUND: The dysbiosis of intestinal microbiota plays an important role in the development of gut-derived infections, making it a potential therapeutic target against multiple organ dysfunction syndrome (MODS) after sepsis. However, the effectiveness of fecal microbiota transplantation (FMT) in treating this disease has been rarely investigated. METHODS: Two male patients, a 65-year-old and an 84-year-old, were initially diagnosed with cerebellar hemorrhage and cerebral infarction, respectively, after admission...
October 18, 2016: Critical Care: the Official Journal of the Critical Care Forum
Young Ha Ahn, Sunyoung Park, Jeong June Choi, Bo-Kyung Park, Kyung Hee Rhee, Eunjoo Kang, Soyeon Ahn, Chul-Ho Lee, Jong Soo Lee, Kyung-Soo Inn, Mi-La Cho, Sung-Hwan Park, Kyunghee Park, Hae Jung Park, Jae Hyun Lee, Jung Won Park, Nam Hoon Kwon, Hyunbo Shim, Byung Woo Han, Pilhan Kim, Joo-Youn Lee, Youngho Jeon, Jin Won Huh, Mirim Jin, Sunghoon Kim
The N-terminal truncated form of a protein synthesis enzyme, tryptophanyl-tRNA synthetase (mini-WRS), is secreted as an angiostatic ligand. However, the secretion and function of the full-length WRS (FL-WRS) remain unknown. Here, we report that the FL-WRS, but not mini-WRS, is rapidly secreted upon pathogen infection to prime innate immunity. Blood levels of FL-WRS were increased in sepsis patients, but not in those with sterile inflammation. FL-WRS was secreted from monocytes and directly bound to macrophages via a toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex to induce phagocytosis and chemokine production...
October 17, 2016: Nature Microbiology
Amanda Fortes Francisco, Shiromani Jayawardhana, Michael D Lewis, Karen L White, David M Shackleford, Gong Chen, Jessica Saunders, Maria Osuna-Cabello, Kevin D Read, Susan A Charman, Eric Chatelain, John M Kelly
The insect-transmitted protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, and infects 5-8 million people in Latin America. Chagas disease is characterised by an acute phase, which is partially resolved by the immune system, but then develops as a chronic life-long infection. There is a consensus that the front-line drugs benznidazole and nifurtimox are more effective against the acute stage in both clinical and experimental settings. However, confirmative studies have been restricted by difficulties in demonstrating sterile parasitological cure...
October 17, 2016: Scientific Reports
Yenis M Gutierrez-Murgas, Gwenn Skar, Danielle Ramirez, Matthew Beaver, Jessica N Snowden
BACKGROUND: Shunt infection is a frequent and serious complication in the surgical treatment in hydrocephalus. Previous studies have shown an attenuated immune response to these biofilm-mediated infections. We proposed that IL-10 reduces the inflammatory response to Staphylococcus epidermidis (S. epidermidis) CNS catheter infection. METHODS: In this study, a murine model of catheter-associated S. epidermidis biofilm infection in the CNS was generated based on a well-established similar model for S...
October 13, 2016: Journal of Neuroinflammation
Stefano Mancini, Carmen Menzi, Frank Oechslin, Philippe Moreillon, José Manuel Entenza
Streptococcus gordonii and related species of oral viridans group streptococci (VGS) are common etiological agents of infective endocarditis (IE). We explored vaccination as a strategy to prevent VGS- IE, using a novel antigen presenting system based on non-genetically modified Lactococcus lactis displaying vaccinogens on its surface.Hsa and PadA are surface-located S. gordonii proteins implicated in platelet adhesion and aggregation, which are key steps in the pathogenesis of IE. This function makes them ideal targets for vaccination against VGS- IE...
October 10, 2016: Infection and Immunity
Eric R Weiss, Galit Alter, Javier Gordon Ogembo, Jennifer L Henderson, Barbara Tabak, Yasin Bakiş, Mohan Somasundaran, Manuel Garber, Liisa Selin, Katherine Luzuriaga
: The Epstein Barr virus (EBV) gp350 glycoprotein interacts with the cellular receptor to mediate viral entry and is thought to be the major target for neutralizing antibodies. To better understand the role of EBV-specific antibodies in the control of viral replication and evolution of sequence diversity, we measured EBV gp350-specific antibody responses and sequenced the gp350 gene in samples obtained from individuals experiencing primary EBV infection (acute infectious mononucleosis; AIM) and again 6 months later (convalescence, CONV)...
October 12, 2016: Journal of Virology
C M Pender, S Kim, T D Potter, M M Ritzi, M Young, R A Dalloul
Coccidiosis is regarded as the parasitic disease with the greatest economic impact on the poultry industry due to reduced performance and increased mortality. A study was conducted to investigate the effects of in ovo administration of probiotics on hatchability, performance, immune organ weights, and lesion scores in broiler chicks during a mixed Eimeria infection. At embryonic day 18, 210 eggs were injected with either sterile water or 1×10(6) cfu probiotic bacteria. On day 3 post-hatch, half of the chicks from each treatment group were challenged with a mixed inoculum of Eimeria acervulina, Eimeria maxima and Eimeria tenella...
October 11, 2016: Beneficial Microbes
Braedon McDonald, Paul Kubes
The sterile inflammatory response (inflammation in the absence of infection) to tissue injury and cell death is required for normal wound healing. However, dysregulated sterile inflammation leads to various acute and chronic inflammatory diseases, including those of the liver and gastrointestinal tract. It is therefore important to increase our understanding of the mechanisms that control physiologic vs pathologic sterile inflammation. We have begun to clarify the cellular and molecular mechanisms that coordinate the innate immune response to tissue damage and cell death in the liver...
October 7, 2016: Gastroenterology
Pierre-Louis Hervé, Delphyne Descamps, Charlotte Deloizy, Véronique Dhelft, Daphné Laubreton, Edwige Bouguyon, Abdelhak Boukadiri, Catherine Dubuquoy, Thibaut Larcher, Pierre-Henri Benhamou, Jean-François Eléouët, Nicolas Bertho, Lucie Mondoulet, Sabine Riffault
To put a Respiratory Syncytial Virus (RSV) vaccine onto the market, new vaccination strategies combining scientific and technical innovations need to be explored. Such a vaccine would also need to be adapted to the vaccination of young children that are the principal victims of acute RSV infection. In the present project, we describe the development and the preclinical evaluation of an original epicutaneous RSV vaccine that combines two technologies: Viaskin® epicutaneous patches as a delivery platform and RSV N-nanorings (N) as a subunit antigen...
October 6, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Zora Melkova, Prakash Shankaran, Michaela Madlenakova, Josef Bodor
HIV-1 infection cannot be cured as it persists in latently infected cells that are targeted neither by the immune system nor by available therapeutic approaches. Consequently, a lifelong therapy suppressing only the actively replicating virus is necessary. The latent reservoir has been defined and characterized in various experimental models and in human patients, allowing research and development of approaches targeting individual steps critical for HIV-1 latency establishment, maintenance, and reactivation...
October 5, 2016: Folia Microbiologica
Natascha Luther, Fatemeh Shahneh, Melanie Brähler, Franziska Krebs, Sven Jäckel, Saravanan Subramaniam, Christian Stanger, Tanja Schönfelder, Bettina Kleis-Fischer, Christoph Reinhardt, Hans C Probst, Philip Wenzel, Katrin Schäfer, Christian Becker
RATIONALE: Immune cells play an important role during the generation and resolution of thrombosis. T cells are powerful regulators of immune and non-immune cell function, however their role in sterile inflammation in venous thrombosis has not been systematically examined. OBJECTIVE: This study investigated the recruitment, activation and inflammatory activity of T cells in deep vein thrombosis (DVT) and its consequences for venous thrombus resolution. METHODS AND RESULTS: CD4(+) and CD8(+) T cells infiltrate the thrombus and vein wall rapidly upon DVT induction and remain in the tissue throughout thrombus resolution...
October 5, 2016: Circulation Research
Angela R M Kurz, Monika Pruenster, Ina Rohwedder, Mahalakshmi Ramadass, Kerstin Schäfer, Ute Harrison, Gabriel Gouveia, Claudia Nussbaum, Roland Immler, Johannes R Wiessner, Andreas Margraf, Dae-Sik Lim, Barbara Walzog, Steffen Dietzel, Markus Moser, Christoph Klein, Dietmar Vestweber, Rainer Haas, Sergio D Catz, Markus Sperandio
Neutrophils need to penetrate the perivascular basement membrane for successful extravasation into inflamed tissue, but this process is incompletely understood. Recent findings have associated mammalian sterile 20-like kinase 1 (MST1) loss of function with a human primary immunodeficiency disorder, suggesting that MST1 may be involved in immune cell migration. Here, we have shown that MST1 is a critical regulator of neutrophil extravasation during inflammation. Mst1-deficient (Mst1-/-) neutrophils were unable to migrate into inflamed murine cremaster muscle venules, instead persisting between the endothelium and the basement membrane...
October 4, 2016: Journal of Clinical Investigation
Matthieu Rousseau, H M Sharon Goh, Sarah Holec, Matthew L Albert, Rohan B H Williams, Molly A Ingersoll, Kimberly A Kline
Catheter-associated urinary tract infections (CAUTI) are the most common hospital-associated infections. Here, we report that bladder catheterization initiated a persistent sterile inflammatory reaction within minutes of catheter implantation. Catheterization resulted in increased expression of genes associated with defense responses and cellular migration, with ensuing rapid and sustained innate immune cell infiltration into the bladder. Catheterization also resulted in hypersensitivity to Enterococcus faecalis and uropathogenic Escherichia coli (UPEC) infection, in which colonization was achieved using an inoculum 100-fold lower than the ID90 for infection of an undamaged urothelium with the same uropathogens...
September 22, 2016: JCI Insight
R A Palomares, D J Hurley, L T Crum, E Rollin, T Collop, A Williard, J Felton, J Parrish, L B Corbeil
The objective of this study was to determine the level and duration of IgG antibodies induced against killed whole Tritrichomonas foetus and T foetus-purified surface antigen (TF1.17) in serum, vaginal, and uterine secretions after systemic immunization of beef cows with a vaccine containing killed whole T foetus. Twenty nonpregnant beef cows were randomly assigned to vaccine or control groups as follows: Vaccine (n = 10): cows received 2 mL of a commercial vaccine containing killed whole T foetus subcutaneously and a 2-mL booster 2 weeks later...
September 6, 2016: Theriogenology
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