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https://www.readbyqxmd.com/read/28331091/ebolaviruses-associated-with-differential-pathogenicity-induce-distinct-host-responses-in-human-macrophages
#1
Judith Olejnik, Adriana Forero, Laure R Deflubé, Adam J Hume, Whitney A Manhart, Andrew Nishida, Andrea Marzi, Michael G Katze, Hideki Ebihara, Angela L Rasmussen, Elke Mühlberger
Ebola virus (EBOV) and Reston virus (RESTV) are members of the Ebolavirus genus which greatly differ in their pathogenicity. While EBOV causes a severe disease in humans characterized by a dysregulated inflammatory response and elevated cytokine and chemokine production, there are no reported disease-associated human cases of RESTV infection, suggesting that RESTV is non-pathogenic for humans. The underlying mechanisms determining the pathogenicity of different ebolavirus species are not yet known. In this study we dissect the host response to EBOV and RESTV infection in primary human monocyte-derived macrophages (MDMs)...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28325863/pharmacological-targeting-of-plasmin-prevents-lethality-in-a-murine-model-of-macrophage-activation-syndrome
#2
Hiroshi Shimazu, Shinya Munakata, Yoshihiko Tashiro, Yousef Salama, Douaa Dhahri, Salita Eiamboonsert, Yasunori Ota, Haruo Onoda, Yuko Tsuda, Yoshio Okada, Hiromitsu Nakauchi, Beate Heissig, Koichi Hattori
Macrophage activation syndrome (MAS) is a life-threatening disorder characterized by a cytokine storm and multiorgan dysfunction due to excessive immune activation. Although abnormalities of coagulation and fibrinolysis are major components of MAS, the role of the fibrinolytic system and its key player, plasmin, in the development of MAS remains to be solved. We established a murine model of fulminant MAS by repeated injections of Toll-like receptor-9 (TLR-9) agonist and D-galactosamine (DG) in immunocompetent mice...
March 21, 2017: Blood
https://www.readbyqxmd.com/read/28320831/interference-of-the-t-cell-and-antigen-presenting-cell-costimulatory-pathway-using-ctla4-ig-abatacept-prevents-staphylococcal-enterotoxin-b-pathology
#3
Sarah J C Whitfield, Chris Taylor, Jane E Risdall, Gareth D Griffiths, James T A Jones, E Diane Williamson, Sjoerd Rijpkema, Luisa Saraiva, Sandrine Vessillier, A Christopher Green, Alun J Carter
Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that binds the receptors in the APC/T cell synapse and causes increased proliferation of T cells and a cytokine storm syndrome in vivo. Exposure to the toxin can be lethal and cause significant pathology in humans. The lack of effective therapies for SEB exposure remains an area of concern, particularly in scenarios of acute mass casualties. We hypothesized that blockade of the T cell costimulatory signal by the CTLA4-Ig synthetic protein (abatacept) could prevent SEB-dependent pathology...
March 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28286804/bacterial-superantigen-toxins-induce-a-lethal-cytokine-storm-by-enhancing-b7-2-cd28-costimulatory-receptor-engagement-a-critical-immune-checkpoint
#4
Raymond Kaempfer, Andrey Popugailo, Revital Levy, Gila Arad, Dalia Hillman, Ziv Rotfogel
Formation of the costimulatory axis between the B7-2 and CD28 coreceptors is critical for T-cell activation. Superantigens, Gram-positive bacterial virulence factors, cause toxic shock and sepsis by hyperinducing inflammatory cytokines. We report a novel role for costimulatory receptors CD28 and B7-2 as obligatory receptors for superantigens, rendering them therapeutic targets. We show that by engaging not only CD28 but also its coligand B7-2 directly, superantigens potently enhance the interaction between B7-2 and CD28, inducing thereby T-cell hyperactivation...
2017: Receptors & Clinical Investigation
https://www.readbyqxmd.com/read/28279802/prevention-of-influenza-virus-induced-bacterial-superinfection-by-standardized-echinacea-purpurea-via-regulation-of-surface-receptor-expression-in-human-bronchial-epithelial-cells
#5
Selvarani Vimalanathan, Roland Schoop, Andy Suter, James Hudson
Viral infections may predispose the airways to secondary bacterial infections that can lead to unfavorable progression of principally self-limiting illnesses. Such complicated respiratory infections include pneumonia, bronchitis, sinusitis, acute otitis media, and sepsis, which cause high morbidity and lethality. Some of the pathogenic consequences of viral infections, like the expression of bacterial adhesion receptors and the disturbance of physical barrier integrity due to inflammation, may create permissive conditions for co-infections...
March 7, 2017: Virus Research
https://www.readbyqxmd.com/read/28277850/diagnosis-and-management-of-catastrophic-antiphospholipid-syndrome
#6
Or Carmi, Maya Berla, Yehuda Shoenfeld, Yair Levy
Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening disease. In 1992, Asherson defined it as a widespread coagulopathy related to the antiphospholipid antibodies (aPL). CAPS requires rapid diagnosis and prompt initiation of treatment. Areas covered: This paper discusses all aspects of CAPS, including its pathophysiology, clinical manifestations, diagnostic approaches, differential diagnoses, management and treatment of relapsing CAPS, and its prognosis. To obtain the information used in this review, scientific databases were searched using the key words antiphospholipid antibodies, catastrophic antiphospholipid syndrome, hemolytic anemia, lupus anticoagulant, and thrombotic microangiopathic hemolytic anemia...
March 13, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28273457/macrophage-death-following-influenza-vaccination-initiates-the-inflammatory-response-that-promotes-dendritic-cell-function-in-the-draining-lymph-node
#7
Nikolaos Chatziandreou, Yagmur Farsakoglu, Miguel Palomino-Segura, Rocco D'Antuono, Diego Ulisse Pizzagalli, Federica Sallusto, Veronika Lukacs-Kornek, Mariagrazia Uguccioni, Davide Corti, Shannon J Turley, Antonio Lanzavecchia, Michael C Carroll, Santiago F Gonzalez
The mechanism by which inflammation influences the adaptive response to vaccines is not fully understood. Here, we examine the role of lymph node macrophages (LNMs) in the induction of the cytokine storm triggered by inactivated influenza virus vaccine. Following vaccination, LNMs undergo inflammasome-independent necrosis-like death that is reliant on MyD88 and Toll-like receptor 7 (TLR7) expression and releases pre-stored interleukin-1α (IL-1α). Furthermore, activated medullary macrophages produce interferon-β (IFN-β) that induces the autocrine secretion of IL-1α...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28272907/emerging-avian-influenza-infections-current-understanding-of-innate-immune-response-and-molecular-pathogenesis
#8
Anamika Mishra, Periyasamy Vijayakumar, Ashwin Ashok Raut
The highly pathogenic avian influenza viruses (HPAIVs) cause severe disease in gallinaceous poultry species, domestic ducks, various aquatic and terrestrial wild bird species as well as humans. The outcome of the disease is determined by complex interactions of multiple components of the host, the virus, and the environment. While the host-innate immune response plays an important role for clearance of infection, excessive inflammatory immune response (cytokine storm) may contribute to morbidity and mortality of the host...
March 8, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28266597/the-protective-effect-of-the-anti-toll-like-receptor-9-antibody-against-acute-cytokine-storm-caused-by-immunostimulatory-dna
#9
Yusuke Murakami, Ryutaro Fukui, Yuji Motoi, Takuma Shibata, Shin-Ichiroh Saitoh, Ryota Sato, Kensuke Miyake
Toll-like Receptor 9 (TLR9) is an innate immune receptor recognizing microbial DNA. TLR9 is also activated by self-derived DNA, such as mitochondrial DNA, in a variety of inflammatory diseases. We show here that TLR9 activation in vivo is controlled by an anti-TLR9 monoclonal Ab (mAb). A newly established mAb, named NaR9, clearly detects endogenous TLR9 expressed in primary immune cells. The mAb inhibited TLR9-dependent cytokine production in vitro by bone marrow-derived macrophages and conventional dendritic cells...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28263892/in-vitro-assays-supporting-the-safety-assessment-of-immunomodulatory-monoclonal-antibodies
#10
Frank R Brennan, Andrea Kiessling
Many monoclonal antibodies (mAbs) licensed for human use or in clinical development for cancer and autoimmune disease directly interact with the immune system. These immunomodulatory mAbs have an inherent risk of adverse immune-mediated drug reactions, including infusion reactions, cytokine storms, immunosuppression and autoimmunity. A thorough understanding of the potential for immunotoxicity of a mAb is required to support administration to humans. This review will highlight the key role of in vitro assays in defining the immunopharmacology, immunotoxicity and immunogenicity of mAbs...
March 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28261486/combined-inhibition-of-c5-and-cd14-efficiently-attenuated-the-inflammatory-response-in-a-porcine-model-of-meningococcal-sepsis
#11
Bernt C Hellerud, Hilde L Orrem, Knut Dybwik, Søren E Pischke, Andreas Baratt-Due, Albert Castellheim, Hilde Fure, Grethe Bergseth, Dorte Christiansen, Miles A Nunn, Terje Espevik, Corinna Lau, Petter Brandtzæg, Erik W Nielsen, Tom E Mollnes
BACKGROUND: Fulminant meningococcal sepsis, characterized by overwhelming innate immune activation, mostly affects young people and causes high mortality. This study aimed to investigate the effect of targeting two key molecules of innate immunity, complement component C5, and co-receptor CD14 in the Toll-like receptor system, on the inflammatory response in meningococcal sepsis. METHODS: Meningococcal sepsis was simulated by continuous intravenous infusion of an escalating dose of heat-inactivated Neisseria meningitidis administered over 3 h...
2017: Journal of Intensive Care
https://www.readbyqxmd.com/read/28250128/pathology-in-permissive-syrian-hamsters-after-infection-with-human-adenovirus-is-the-result-of-virus-replication-hadv-c6-replicates-more-and-causes-more-pathology-than-hadv-c5
#12
Ann E Tollefson, Baoling Ying, Jacqueline F Spencer, John E Sagartz, William S M Wold, Karoly Toth
Syrian hamsters are permissive for the replication of species C human adenoviruses. The virus replicates to high titers in the liver of these animals after intravenous infection, while respiratory infection results in virus replication in the lung. Here we show that two types belonging to species C, HAdV-C5 and HAdV-C6, replicate to a significantly different extent and cause pathology with significantly different severity, with HAdV-C6 replicating better and inducing more severe and more widespread lesions...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28237664/il-10-deficient-mice-express-ifn-%C3%AE-mrna-and-clear-leptospira-interrogans-from-their-kidneys-more-rapidly-than-normal-c57bl-6-mice
#13
Amy A Devlin, Priya J Halvorsen, Jennifer C Miller, Scott M Laster
Leptospira interrogans (L. interrogans), the causative agent of leptospirosis, is a widespread zoonotic spirochete that lives a dual lifestyle. L. interrogans infects mice, rats, and wildlife in a persistent and asymptomatic fashion, while also causing productive and acute infections in other mammals such as humans and hamsters. Infections in humans can be fatal, accompanied by a cytokine storm and shock-like symptoms. Production of IL-10 has been noted in both rodent and human infections which has led a number of investigators to hypothesize that IL-10 plays a role in the pathogenesis of this disease...
February 10, 2017: Immunobiology
https://www.readbyqxmd.com/read/28236842/conditional-potency-is-a-hallmark-of-viral-protein-derived-toxic-peptides
#14
Man Tang, Xiaoxia Li, Qizhang Li, Yanchao Zhou, Wen Pan, Jiayang Gao, Zi-Wei Ye, Shaoping Weng, Qiuyun Liu, Jianguo He, Zhumei He
Viral infections are major ongoing challenges to mankind. The theory of cytokine storm cannot fully account for the virulence of some highly infectious viruses with high mortality rates. Although numerous viruses are capable of lysing animal and human cells in vivo, viral protein-derived peptides are mostly mild in standard culture conditions in in vitro assays. A hypothesis is postulated that conditional potency of viral protein-derived toxic peptides could at least in part explain cell senescence upon viral infections...
March 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28219889/rapid-and-rigorous-il-17a-production-by-a-distinct-subpopulation-of-effector-memory-t-lymphocytes-constitutes-a-novel-mechanism-of-toxic-shock-syndrome-immunopathology
#15
Peter A Szabo, Ankur Goswami, Delfina M Mazzuca, Kyoungok Kim, David B O'Gorman, David A Hess, Ian D Welch, Howard A Young, Bhagirath Singh, John K McCormick, S M Mansour Haeryfar
Toxic shock syndrome (TSS) is caused by staphylococcal and streptococcal superantigens (SAgs) that provoke a swift hyperinflammatory response typified by a cytokine storm. The precipitous decline in the host's clinical status and the lack of targeted therapies for TSS emphasize the need to identify key players of the storm's initial wave. Using a humanized mouse model of TSS and human cells, we herein demonstrate that SAgs elicit in vitro and in vivo IL-17A responses within hours. SAg-triggered human IL-17A production was characterized by remarkably high mRNA stability for this cytokine...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28217930/cytokine-storm-syndrome-looking-toward-the-precision-medicine-era
#16
REVIEW
Edward M Behrens, Gary A Koretzky
No abstract text is available yet for this article.
February 19, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28206702/statistical-issues-in-first-in-human-studies-on-bia-10-2474-neglected-comparison-of-protocol-against-practice
#17
Sheila M Bird, Rosemary A Bailey, Andrew P Grieve, Stephen Senn
By setting the regulatory-approved protocol for a suite of first-in-human studies on BIA 10-2474 against the subsequent French investigations, we highlight 6 key design and statistical issues, which reinforce recommendations by a Royal Statistical Society Working Party, which were made in the aftermath of cytokine release storm in 6 healthy volunteers in the United Kingdom in 2006. The 6 issues are dose determination, availability of pharmacokinetic results, dosing interval, stopping rules, appraisal by safety committee, and clear algorithm required if combining approvals for single and multiple ascending dose studies...
March 2017: Pharmaceutical Statistics
https://www.readbyqxmd.com/read/28198028/proinflammatory-chemokines-are-major-mediators-of-exuberant-immune-response-associated-with-influenza-a-h1n1-pdm09-virus-infection
#18
Maria Thomas, Reeta Subramaniam Mani, Mariamma Philip, Ranjeeta Adhikary, Sangeeta Joshi, Srigiri S Revadi, Shashidhar Buggi, Anita Desai, Ravi Vasanthapuram
In India, the case fatality ratio of the pandemic A (H1N1) pdm09 influenza was relatively higher when compared to seasonal influenza A infection. Hypercytokinemia or "cytokine storm" has been previously implicated in the pathogenesis of other influenza viruses. The present study was undertaken to compare the cytokine profiles of A (H1N1) pdm09 influenza and seasonal H3 infection in Indian population and to correlate the findings with disease severity. Plasma levels of 18 cytokines/chemokines were measured by flow-cytometry using a bead based assay in patients infected with A (H1N1) pdm09 virus (n = 96) and Influenza A seasonal H3 virus (n = 30) categorised into mild, moderate and severe groups along with healthy controls (n = 36)...
February 15, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28197626/kdm6a-and-kdm6b-altered-expression-in-malignant-pleural-mesothelioma
#19
Sian Cregan, Maeve Breslin, Gerard Roche, Sigrid Wennstedt, Lauren MacDonagh, Cinaria Albadri, Yun Gao, Kenneth J O'Byrne, Sinead Cuffe, Stephen P Finn, Steven G Gray
Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura primarily associated with prior exposure to asbestos. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Inflammation is thought to be a key element in the pathogenesis of MPM, and recently Kdm6 family members (Kdm6a and Kdm6b) have been identified as playing important roles in inflammatory processes...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28135567/tafro-syndrome-new-subtype-of-idiopathic-multicentric-castleman-disease
#20
REVIEW
Gordan Srkalovic, Inga Marijanovic, Maya B Srkalovic, David C Fajgenbaum
Castleman disease (CD) describes a group of three rare and poorly understood lymphoproliferative disorders that have heterogeneous clinical symptoms and common lymph node histopathological features. Unicentric CD (UCD) involves a single region of enlarged nodes. Multicentric CD (MCD) involves multiple regions of enlarged lymph nodes, constitutional symptoms, and organ dysfunction due to a cytokine storm often including interleukin 6. MCD is further divided into Human Herpes Virus-8 (HHV-8)-associated MCD, which occurs in immunocompromised individuals, and HHV-8-negative/idiopathic MCD (iMCD)...
January 26, 2017: Bosnian Journal of Basic Medical Sciences
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