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Sterile immunity

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https://www.readbyqxmd.com/read/28223498/attenuated-pfspz-vaccine-induces-strain-transcending-t-cells-and-durable-protection-against-heterologous-controlled-human-malaria-infection
#1
Kirsten E Lyke, Andrew S Ishizuka, Andrea A Berry, Sumana Chakravarty, Adam DeZure, Mary E Enama, Eric R James, Peter F Billingsley, Anusha Gunasekera, Anita Manoj, Minglin Li, Adam J Ruben, Tao Li, Abraham G Eappen, Richard E Stafford, Natasha Kc, Tooba Murshedkar, Floreliz H Mendoza, Ingelise J Gordon, Kathryn L Zephir, LaSonji A Holman, Sarah H Plummer, Cynthia S Hendel, Laura Novik, Pamela J M Costner, Jamie G Saunders, Nina M Berkowitz, Barbara J Flynn, Martha C Nason, Lindsay S Garver, Matthew B Laurens, Christopher V Plowe, Thomas L Richie, Barney S Graham, Mario Roederer, B Kim Lee Sim, Julie E Ledgerwood, Stephen L Hoffman, Robert A Seder
A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. No injectable malaria vaccine has demonstrated long-term protection against CHMI using Pf parasites heterologous to the vaccine strain. Here, we conducted an open-label trial with PfSPZ Vaccine at a dose of 9.0 × 10(5) PfSPZ administered i...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28222903/modified-mrna-vaccines-protect-against-zika-virus-infection
#2
Justin M Richner, Sunny Himansu, Kimberly A Dowd, Scott L Butler, Vanessa Salazar, Julie M Fox, Justin G Julander, William W Tang, Sujan Shresta, Theodore C Pierson, Giuseppe Ciaramella, Michael S Diamond
The emergence of ZIKV infection has prompted a global effort to develop safe and effective vaccines. We engineered a lipid nanoparticle (LNP) encapsulated modified mRNA vaccine encoding wild-type or variant ZIKV structural genes and tested immunogenicity and protection in mice. Two doses of modified mRNA LNPs encoding prM-E genes that produced virus-like particles resulted in high neutralizing antibody titers (∼1/100,000) that protected against ZIKV infection and conferred sterilizing immunity. To offset a theoretical concern of ZIKV vaccines inducing antibodies that cross-react with the related dengue virus (DENV), we designed modified prM-E RNA encoding mutations destroying the conserved fusion-loop epitope in the E protein...
February 16, 2017: Cell
https://www.readbyqxmd.com/read/28222180/pre-existing-neutralizing-antibody-mitigates-b-cell-dysregulation-and-enhances-the-env-specific-antibody-response-in-shiv-infected-rhesus-macaques
#3
Juan Pablo Jaworski, Peter Bryk, Zachary Brower, Bo Zheng, Ann J Hessell, Alexander F Rosenberg, Tong Tong Wu, Ignacio Sanz, Michael C Keefer, Nancy L Haigwood, James J Kobie
Our central hypothesis is that protection against HIV infection will be powerfully influenced by the magnitude and quality of the B cell response. Although sterilizing immunity, mediated by pre-formed abundant and potent antibodies is the ultimate goal for B cell-targeted HIV vaccine strategies, scenarios that fall short of this may still confer beneficial defenses against viremia and disease progression. We evaluated the impact of sub-sterilizing pre-existing neutralizing antibody on the B cell response to SHIV infection...
2017: PloS One
https://www.readbyqxmd.com/read/28219890/local-tnfr1-signaling-licenses-murine-neutrophils-for-increased-tlr-dependent-cytokine-and-eicosanoid-production
#4
Jacques Deguine, Jessica Wei, Roman Barbalat, Karsten Gronert, Gregory M Barton
Neutrophils are generally the first immune cells recruited during the development of sterile or microbial inflammation. As these cells express many innate immune receptors with the potential to directly recognize microbial or endogenous signals, we set out to assess whether their functions are locally influenced by the signals present at the onset of inflammation. Using a mouse model of peritonitis, we demonstrate that neutrophils elicited in the presence of C-type lectin receptor ligands have an increased ability to produce cytokines, chemokines, and lipid mediators in response to subsequent TLR stimulation...
February 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28215278/nucleic-acid-immunity
#5
G Hartmann
Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its function and replication. Tremendous progress has been made in the understanding of these mechanisms which keep foreign or unwanted nucleic acids from viruses or phages in check. Mechanisms reach from restriction-modification systems and CRISPR/Cas in bacteria and archaea to RNA interference and immune sensing of nucleic acids, altogether integral parts of a system which is now appreciated as nucleic acid immunity...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28213094/aspirin-triggered-resolvin-d1-modified-materials-promote-the-accumulation-of-pro-regenerative-immune-cell-subsets-and-enhance-vascular-remodeling
#6
Mary Caitlin P Sok, Maxianne C Tria, Claire E Olingy, Cheryl L San Emeterio, Edward A Botchwey
: Many goals in tissue engineering rely on modulating cellular localization and polarization of cell signaling, including the inhibition of inflammatory infiltrate, facilitation of inflammatory cell egress, and clearance of apoptotic cells. Omega-3 polyunsaturated fatty acid-derived resolvins are gaining increasing recognition for their essential roles in inhibition of neutrophil invasion into inflamed tissue and promotion of macrophage phagocytosis of cellular debris as well as their egress to the lymphatics...
February 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28210784/novel-aids-therapies-based-on-gene-editing
#7
REVIEW
Kamel Khalili, Martyn K White, Jeffrey M Jacobson
HIV/AIDS remains a major public health issue. In 2014, it was estimated that 36.9 million people are living with HIV worldwide, including 2.6 million children. Since the advent of combination antiretroviral therapy (cART), in the 1990s, treatment has been so successful that in many parts of the world, HIV has become a chronic condition in which progression to AIDS has become increasingly rare. However, while people with HIV can expect to live a normal life span with cART, lifelong medication is required and cardiovascular, renal, liver, and neurologic diseases are still possible, which continues to prompt research for a cure for HIV...
February 16, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28209603/deoxyribonuclease-partially-ameliorates-thioacetamide-induced-hepatorenal-injury
#8
Lenka Vokálová, Lucia Lauková, Jozef Čonka, Veronika Melišková, Veronika Borbélyová, Janka Bábíčková, Ľubomíra Tóthová, Július Hodosy, Barbora Vlková, Peter Celec
Several recent studies have shown that liver injury is associated with the release of DNA from hepatocytes. This DNA stimulates innate immunity and induces sterile inflammation exacerbating the liver damage. Similar mechanisms have been described for acute renal injury. Deoxyribonuclease degrades cell-free DNA and can potentially prevent some of the induced tissue damage. In this study the effects of thioacetamide-induced hepatorenal injury on plasma DNA in rats were analysed. Plasma DNA of both nuclear and mitochondrial origin was higher in thioacetamide-treated animals...
February 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28207901/yope-specific-cd8-t-cells-provide-protection-against-systemic-and-mucosal-yersinia-pseudotuberculosis-infection
#9
Norberto González-Juarbe, Haiqian Shen, Molly A Bergman, Carlos J Orihuela, Peter H Dube
Prior studies indicated that CD8+ T cells responding to a surrogate single antigen expressed by Y. pseudotuberculosis, ovalbumin, were insufficient to protect against yersiniosis. Herein we tested the hypothesis that CD8+ T cells reactive to the natural Yersinia antigen YopE would be more effective at providing mucosal protection. We first confirmed that immunization with the attenuated ksgA- strain of Y. pseudotuberculosis generated YopE-specific CD8+ T cells. These T cells were protective against challenge with virulent Listeria monocytogenes expressing secreted YopE...
2017: PloS One
https://www.readbyqxmd.com/read/28199305/sterile-protection-against-human-malaria-by-chemoattenuated-pfspz-vaccine
#10
Benjamin Mordmüller, Güzin Surat, Heimo Lagler, Sumana Chakravarty, Andrew S Ishizuka, Albert Lalremruata, Markus Gmeiner, Joseph J Campo, Meral Esen, Adam J Ruben, Jana Held, Carlos Lamsfus Calle, Juliana B Mengue, Tamirat Gebru, Javier Ibáñez, Mihály Sulyok, Eric R James, Peter F Billingsley, K C Natasha, Anita Manoj, Tooba Murshedkar, Anusha Gunasekera, Abraham G Eappen, Tao Li, Richard E Stafford, Minglin Li, Phil L Felgner, Robert A Seder, Thomas L Richie, B Kim Lee Sim, Stephen L Hoffman, Peter G Kremsner
A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (PfSPZ) inoculated by mosquitoes; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ ('PfSPZ Vaccine'); or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine or mefloquine (chemoprophylaxis with sporozoites)...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28192059/inflammasomes-key-mediators-of-lung-immunity
#11
Judie A Howrylak, Kiichi Nakahira
Inflammasomes are key inflammatory signaling platforms that detect microbial substances, sterile environmental insults, and molecules derived from host cells. Activation of the inflammasome promotes caspase-1-mediated secretion of proinflammatory cytokines interleukin (IL)-1β and IL-18 and pyroptosis. Recent developments in this field demonstrate the crucial role of the inflammasome in a wide range of disease models. Although inflammasomes are a crucial part of host defense mechanisms against pathogens, the exuberant immune response resulting from inflammasome activation also contributes to the development of various diseases...
February 10, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/28191008/the-nlrp3-and-pyrin-inflammasomes-implications-in-the-pathophysiology-of-autoinflammatory-diseases
#12
REVIEW
Carlos de Torre-Minguela, Pablo Mesa Del Castillo, Pablo Pelegrín
Inflammasomes are multiprotein complexes that critically control different aspects of innate and adaptive immunity. Among them we could highlight the release of pro-inflammatory cytokines that induce and maintain the inflammatory response. Usually, inflammasomes result from oligomerization of a nucleotide-binding domain-like receptor (NLR) after sensing different pathogenic or endogenous sterile dangerous signals; however, other proteins such as absent in melanoma 2, retinoic acid-inducible gene I, or pyrin could also form inflammasome platforms...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28188224/lung-pericyte-like-cells-are-functional-immune-sentinel-cells
#13
Chi F Hung, Kristen L Mittelsteadt, Rena Brauer, Bonnie L McKinney, Teal S Hallstrand, William C Parks, Peter Chen, Lynn M Schnapp, W Conrad Liles, Jeremy S Duffield, William A Altemeier
Pericytes are perivascular PDGFRβ+ stromal cells required for vasculogenesis and maintenance of microvascular homeostasis in many organs. Because of their unique juxtaposition to microvascular endothelium, lung PDGFRβ+ cells are well situated to detect pro-inflammatory molecules released following epithelial injury and promote acute inflammatory responses. Thus, we hypothesized that these cells represent an unrecognized immune surveillance or injury-sentinel interstitial cell. To evaluate this hypothesis, we isolated PDGFRβ+ cells from murine lung and demonstrated that they have characteristics consistent with a pericyte population (referred to as pericyte-like cells for simplicity hereafter)...
February 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28181006/cyclic-dinucleotides-in-the-scope-of-the-mammalian-immune-system
#14
Arun K Mankan, Martina Müller, Gregor Witte, Veit Hornung
First discovered in prokaryotes and more recently in eukaryotes, cyclic dinucleotides (CDNs) constitute a unique branch of second messenger signaling systems. Within prokaryotes CDNs regulate a wide array of different biological processes, whereas in the vertebrate system CDN signaling is largely dedicated to activation of the innate immune system. In this book chapter we summarize the occurrence and signaling pathways of these small-molecule second messengers, most importantly in the scope of the mammalian immune system...
February 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28179497/multicenter-systems-analysis-of-human-blood-reveals-immature-neutrophils-in-males-and-during-pregnancy
#15
Jana Blazkova, Sarthak Gupta, Yudong Liu, Brice Gaudilliere, Edward A Ganio, Christopher R Bolen, Ron Saar-Dover, Gabriela K Fragiadakis, Martin S Angst, Sarfaraz Hasni, Nima Aghaeepour, David Stevenson, Nicole Baldwin, Esperanza Anguiano, Damien Chaussabel, Matthew C Altman, Mariana J Kaplan, Mark M Davis, David Furman
Despite clear differences in immune system responses and in the prevalence of autoimmune diseases between males and females, there is little understanding of the processes involved. In this study, we identified a gene signature of immature-like neutrophils, characterized by the overexpression of genes encoding for several granule-containing proteins, which was found at higher levels (up to 3-fold) in young (20-30 y old) but not older (60 to >89 y old) males compared with females. Functional and phenotypic characterization of peripheral blood neutrophils revealed more mature and responsive neutrophils in young females, which also exhibited an elevated capacity in neutrophil extracellular trap formation at baseline and upon microbial or sterile autoimmune stimuli...
February 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28178282/trypanosoma-cruzi-high-mobility-group-b-tchmgb-can-act-as-an-inflammatory-mediator-on-mammalian-cells
#16
Pamela Cribb, Virginia Perdomo, Victoria L Alonso, Romina Manarin, Jorge Barrios-Payán, Brenda Marquina-Castillo, Luis Tavernelli, Rogelio Hernández-Pando
BACKGROUND: High Mobility Group B (HMGB) proteins are nuclear architectural factors involved in chromatin remodeling and important nuclear events. HMGBs also play key roles outside the cell acting as alarmins or Damage-associated Molecular Patterns (DAMPs). In response to a danger signal these proteins act as immune mediators in the extracellular milieu. Moreover, these molecules play a central role in the pathogenesis of many autoimmune and both infectious and sterile inflammatory chronic diseases...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28167070/regulation-by-gut-bacteria-of-immune-response-bacillus-thuringiensis-susceptibility-and-hemolin-expression-in-plodia-interpunctella
#17
Alonso A Orozco-Flores, Jose A Valadez-Lira, Brenda Oppert, Ricardo Gomez-Flores, Reyes Tamez-Guerra, Cristina Rodríguez-Padilla, Patricia Tamez-Guerra
Plodia interpunctella (Hübner) is an important stored grain insect pest worldwide, and the first lepidopteran with reported resistance to Bacillus thuringiensis (Bt) toxins. Since gut bacteria may affect Bt insecticidal activity, we evaluated whether P. interpunctella lacking gut bacteria had differences in immune responses and susceptibility to the Bt formulation, Bactospeine. In order to clear gut bacteria, third instar larvae were reared on artificial diet containing antibiotics, or were obtained from sterilized eggs and reared under sterile conditions, and larvae were fed diets with or without Bt...
February 3, 2017: Journal of Insect Physiology
https://www.readbyqxmd.com/read/28163301/homeostasis-altering-molecular-processes-as-mechanisms-of-inflammasome-activation
#18
REVIEW
Adrian Liston, Seth L Masters
The innate immune system uses a distinct set of germline-encoded pattern recognition receptors (PRRs) to initiate downstream inflammatory cascades. This recognition system is in stark contrast to the adaptive immune system, which relies on highly variable, randomly generated antigen receptors. A key limitation of the innate immune system's reliance on fixed PRRs is its inflexibility in responding to rapidly evolving pathogens. Recent advances in our understanding of inflammasome activation suggest that the innate immune system also has sophisticated mechanisms for responding to pathogens for which there is no fixed PRR...
February 6, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28162008/clinical-implications-of-understanding-the-association-between-oxidative-stress-and-pediatric-nafld
#19
Jake P Mann, Massimiliano Raponi, Valerio Nobili
Oxidative stress is central to the pathogenesis of non-alcoholic steatohepatitis. The reactive oxygen species (ROS) that characterise oxidative stress are generated in several cellular sites and their production is influence by multi-organ interactions. Areas covered: Mitochondrial dysfunction is the main source of ROS in fatty liver and is closely related to endoplasmic reticulum stress. Both are caused by lipotoxicity and together these three factors form a cycle of progressive organelle damage, resulting in sterile inflammation and apoptosis...
February 6, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28159592/the-hematopoiesis-in-gill-and-its-role-in-the-immune-response-of-pacific-oyster-crassostrea-gigas-against-secondary-challenge-with-vibrio-splendidus
#20
Yiqun Li, Xiaorui Song, Weilin Wang, Lingling Wang, Qilin Yi, Shuai Jiang, Zhihao Jia, Xinyu Du, Limei Qiu, Linsheng Song
Increasing evidences have demonstrated that the invertebrate gill is a predominant tissue participating in the immune response during pathogen challenge. In the present study, the hematopoiesis and immune activities in gill of Pacific oyster Crassostrea gigas were investigated. Stem-like cells with big nuclei and thin cytoplasm were found in the tubules of gill filaments, where DNA synthesis is active and hemocytes production are exuberant. The oysters primarily stimulated by formaldehyde-killed Vibrio splendidus exhibited stronger immune responses and enhanced cell regeneration in gill when they encountered the secondary challenge of live V...
February 1, 2017: Developmental and Comparative Immunology
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