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Adaptive immune system

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https://www.readbyqxmd.com/read/28445638/antigenic-gm3-lactone-mimetic-molecule-integrated-mannosylated-glycopeptide-nanofibers-for-the-activation-and-maturation-of-dendritic-cells
#1
Gokhan Gunay, Melis Sardan Ekiz, Xhenti Ferhati, Barbara Richichi, Cristina Nativi, Ayse Begum Tekinay, Mustafa O Guler
The ability of dendritic cells to coordinate innate and adaptive immune responses makes them essential targets for vaccination strategies. Presentation of specific antigens by dendritic cells is required for the activation of the immune system against many pathogens, and nanoscale materials can be functionalized for active targeting of dendritic cells. In this work, we integrated an immunogenic, carbohydrate melanoma-associated antigen-mimetic GM3-lactone molecule into mannosylated peptide amphiphile nanofibers to target dendritic cells through DC-SIGN receptor...
April 26, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28445522/revealing-phenotype-associated-functional-differences-by-genome-wide-scan-of-ancient-haplotype-blocks
#2
Ritsuko Onuki, Rui Yamaguchi, Tetsuo Shibuya, Minoru Kanehisa, Susumu Goto
Genome-wide scans for positive selection have become important for genomic medicine, and many studies aim to find genomic regions affected by positive selection that are associated with risk allele variations among populations. Most such studies are designed to detect recent positive selection. However, we hypothesize that ancient positive selection is also important for adaptation to pathogens, and has affected current immune-mediated common diseases. Based on this hypothesis, we developed a novel linkage disequilibrium-based pipeline, which aims to detect regions associated with ancient positive selection across populations from single nucleotide polymorphism (SNP) data...
2017: PloS One
https://www.readbyqxmd.com/read/28444390/characterisation-of-drug-specific-signalling-between-primary-human-hepatocytes-and-immune-cells
#3
Monday O Ogese, Lee Faulkner, Roz E Jenkins, Neil S French, Ian M Copple, Daniel J Antoine, Mohamed Elmasry, Hasan Malik, Christopher E Goldring, B Kevin Park, Catherine Betts, Dean J Naisbitt
It is now apparent that antigen-specific T-cells are activated in certain patients with drug-induced liver injury (DILI). Since cross-talk between hepatocytes and immune cells is likely to be critical in determining the outcome of drug exposure, the aim of this study was to profile the signals released by drug-treated hepatocytes and to characterise the impact of these molecules on dendritic cells. Human hepatocytes were exposed to three drugs (flucloxacillin, amoxicillin and isoniazid) associated with DILI potentially mediated by the adaptive immune system as drug-specific T-cells have been isolated from DILI patients, and the metabolite nitroso-sulfamethoxazole (SMX-NO)...
April 21, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28443246/genetic-and-dietary-iron-overload-differentially-affect-the-course-of-salmonella-typhimurium-infection
#4
Manfred Nairz, Andrea Schroll, David Haschka, Stefanie Dichtl, Piotr Tymoszuk, Egon Demetz, Patrizia Moser, Hubertus Haas, Ferric C Fang, Igor Theurl, Günter Weiss
Genetic and dietary forms of iron overload have distinctive clinical and pathophysiological features. HFE-associated hereditary hemochromatosis is characterized by overwhelming intestinal iron absorption, parenchymal iron deposition, and macrophage iron depletion. In contrast, excessive dietary iron intake results in iron deposition in macrophages. However, the functional consequences of genetic and dietary iron overload for the control of microbes are incompletely understood. Using Hfe(+/+) and Hfe(-/-) mice in combination with oral iron overload in a model of Salmonella enterica serovar Typhimurium infection, we found animals of either genotype to induce hepcidin antimicrobial peptide expression and hypoferremia following systemic infection in an Hfe-independent manner...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28443099/a-century-of-radiation-therapy-and-adaptive-immunity
#5
REVIEW
Dörthe Schaue
The coming of age for immunotherapy (IT) as a genuine treatment option for cancer patients through the development of new and effective agents, in particular immune checkpoint inhibitors, has led to a huge renaissance of an old idea, namely to harness the power of the immune system to that of radiation therapy (RT). It is not an overstatement to say that the combination of RT with IT has provided a new conceptual platform that has re-energized the field of radiation oncology as a whole. One only has to look at the immense rise in sessions at professional conferences and in grant applications dealing with this topic to see its emergence as a force, while the number of published reviews on the topic is staggering...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28442794/innate-and-adaptive-immunity-shape-circulating-hcv-strains
#6
Silvana Gaudieri, Michaela Lucas
An unbiased genome-to-genome analysis in chronic hepatitis C virus (HCV) infection confirms the innate and adaptive arms of the immune system as drivers of viral evolution. Viral adaptation has a critical role in the interaction between host and pathogen and has important clinical implications for infection outcome.
April 26, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28442752/zika-virus-infection-reprograms-global-transcription-of-host-cells-to-allow-sustained-infection
#7
Shashi Kant Tiwari, Jason Dang, Yue Qin, Gianluigi Lichinchi, Vikas Bansal, Tariq M Rana
Zika virus (ZIKV) is an emerging virus causally linked to neurological disorders, including congenital microcephaly and Guillain-Barré syndrome. There are currently no targeted therapies for ZIKV infection. To identify novel antiviral targets and to elucidate the mechanisms by which ZIKV exploits the host cell machinery to support sustained replication, we analyzed the transcriptomic landscape of human microglia, fibroblast, embryonic kidney and monocyte-derived macrophage cell lines before and after ZIKV infection...
April 26, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28442716/a-puccinia-striiformis-f-sp-tritici-secreted-protein-activates-plant-immunity-at-the-cell-surface
#8
Bayantes Dagvadorj, Ahmet Caglar Ozketen, Ayse Andac, Cian Duggan, Tolga Osman Bozkurt, Mahinur S Akkaya
Pathogens secrete effector proteins to suppress host immunity, mediate nutrient uptake and subsequently enable parasitism. However, on non-adapted hosts, effectors can be detected as non-self by host immune receptors and activate non-host immunity. Nevertheless, the molecular mechanisms of effector triggered non-host resistance remain unknown. Here, we report that a small cysteine-rich protein PstSCR1 from the wheat rust pathogen Puccinia striiformis f. sp. tritici (Pst) activates immunity in the non-host solanaceous model plant Nicotiana benthamiana...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28441401/ancient-genes-establish-stress-induced-mutation-as-a-hallmark-of-cancer
#9
Luis Cisneros, Kimberly J Bussey, Adam J Orr, Milica Miočević, Charles H Lineweaver, Paul Davies
Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms should have evolved with or after the emergence of multicellularity. This leads to two related, but distinct hypotheses: 1) Somatic mutations in cancer will occur in genes that are younger than the emergence of multicellularity (1000 million years [MY]); and 2) genes that are frequently mutated in cancer and whose mutations are functionally important for the emergence of the cancer phenotype evolved within the past 1000 million years, and thus would exhibit an age distribution that is skewed to younger genes...
2017: PloS One
https://www.readbyqxmd.com/read/28440027/the-crispr-cas9-system-their-delivery-in-vivo-and-ex-vivo-applications-and-clinical-development-by-startups
#10
REVIEW
Minjung Song
The CRISPR/Cas9 gene editing system was originally derived from the prokaryotic adaptive immune system mediated by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated proteins (Cas). The system has been successfully applied to genome editing in eukaryotes and has contributed to remarkable advances in the life sciences, in areas ranging from agriculture to genetic disease therapies. For efficient editing and extending the influence of this system, proper delivery of its components is crucial...
April 25, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28439501/the-cell-biology-of-the-trichosporon-host-interaction
#11
REVIEW
Cláudio Duarte-Oliveira, Fernando Rodrigues, Samuel M Gonçalves, Gustavo H Goldman, Agostinho Carvalho, Cristina Cunha
Fungi of the genus Trichosporon are increasingly recognized as causative agents of superficial and invasive fungal disease in humans. Although most species are considered commensals of the human skin and gastrointestinal tract, these basidiomycetes are an increasing cause of fungal disease among immunocompromised hosts, such as hematological patients and solid organ transplant recipients. The initiation of commensal or pathogenic programs by Trichosporon spp. involves the adaptation to the host microenvironment and its immune system...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28438998/cas1-and-the-csy-complex-are-opposing-regulators-of-cas2-3-nuclease-activity
#12
MaryClare F Rollins, Saikat Chowdhury, Joshua Carter, Sarah M Golden, Royce A Wilkinson, Joseph Bondy-Denomy, Gabriel C Lander, Blake Wiedenheft
The type I-F CRISPR adaptive immune system in Pseudomonas aeruginosa (PA14) consists of two CRISPR loci and six CRISPR-associated (cas) genes. Type I-F systems rely on a CRISPR RNA (crRNA)-guided surveillance complex (Csy complex) to bind foreign DNA and recruit a trans-acting nuclease (i.e., Cas2/3) for target degradation. In most type I systems, Cas2 and Cas3 are separate proteins involved in adaptation and interference, respectively. However, in I-F systems, these proteins are fused into a single polypeptide...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438184/microbiota-activated-cd103-dcs-stemming-from-microbiota-adaptation-specifically-drive-%C3%AE-%C3%AE-t17-proliferation-and-activation
#13
Chris Fleming, Yihua Cai, Xuan Sun, Venkatakrishna R Jala, Feng Xue, Samantha Morrissey, Yu-Ling Wei, Yueh-Hsiu Chien, Huang-Ge Zhang, Bodduluri Haribabu, Jian Huang, Jun Yan
BACKGROUND: IL-17-producing γδT cells (γδT17) promote autoinflammatory diseases and cancers. Yet, γδT17 peripheral regulation has not been thoroughly explored especially in the context of microbiota-host interaction. The potent antigen-presenting CD103(+) dendritic cell (DC) is a key immune player in close contact with both γδT17 cells and microbiota. This study presents a novel cellular network among microbiota, CD103(+) DCs, and γδT17 cells. METHODS: Immunophenotyping of IL-17r(-/-) mice and IL-17r(-/-) IRF8(-/-) mice were performed by ex vivo immunostaining and flow cytometric analysis...
April 24, 2017: Microbiome
https://www.readbyqxmd.com/read/28435136/chitosan-enhances-nanoparticle-delivery-from-the-reproductive-tract-to-target-draining-lymphoid-organs
#14
Jaehyung Park, Renuka Ramanathan, Linhchi Pham, Kim A Woodrow
To prime adaptive immune responses from the female reproductive tract (FRT), particulate antigens must be transported to draining lymph nodes (dLNs) since there are no local organized lymphoid structures equivalent to those found in the respiratory or gastrointestinal tracts. However, little is known about how to safely and effectively navigate successive barriers to transport such as crossing the epithelium and gaining access to migratory cells and lymphatic drainage that provide entry into dLNs. Here, we demonstrate that intravaginal pre-treatment with chitosan significantly facilitates translocation of nanoparticles (NPs) across the multilayered vaginal epithelium to target dLNs...
April 20, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28434399/the-next-generation-of-immunotherapy-keeping-lung-cancer-in-check
#15
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28432872/human-effector-memory-t-helper-cells-engage-with-mouse-macrophages-and-cause-graft-versus-host-like-pathology-in-skin-of-humanized-mice-used-in-a-nonclinical-immunization-study
#16
Bala S Sundarasetty, Valery Volk, Sebastian J Theobald, Susanne Rittinghausen, Dirk Schaudien, Vanessa Neuhaus, Constanca Figueiredo, Andreas Schneider, Laura Gerasch, Adele Mucci, Thomas Moritz, Constantin von Kaisenberg, Loukia M Spineli, Katherina Sewald, Armin Braun, Henning Weigt, Arnold Ganser, Renata Stripecke
Humanized mice engrafted with human hematopoietic stem cells and developing functional human T-cell adaptive responses are in critical demand to test human-specific therapeutics. We previously showed that humanized mice immunized with long-lived induced-dendritic cells loaded with the pp65 viral antigen (iDCpp65) exhibited a faster development and maturation of T cells. Herein, we evaluated these effects in a long-term (36 weeks) nonclinical model using two stem cell donors to assess efficacy and safety. Relative to baseline, iDCpp65 immunization boosted the output of effector memory CD4(+) T cells in peripheral blood and lymph nodes...
April 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28432664/human-perinatal-immunity-in-physiological-conditions-and-during-infection
#17
REVIEW
Gijs T J van Well, Leonie A Daalderop, Tim Wolfs, Boris W Kramer
The intrauterine environment was long considered sterile. However, several infectious threats are already present during fetal life. This review focuses on the postnatal immunological consequences of prenatal exposure to microorganisms and related inflammatory stimuli. Both the innate and adaptive immune systems of the fetus and neonate are immature, which makes them highly susceptible to infections. There is good evidence that prenatal infections are a primary cause of preterm births. Additionally, the association between antenatal inflammation and adverse neonatal outcomes has been well established...
December 2017: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/28432131/do-the-microbiota-influence-vaccines-and-protective-immunity-to-pathogens-if-so-is-there-potential-for-efficacious-microbiota-based-vaccines
#18
Dan R Littman
The gut-resident constituents of the microbiota protect the mucosa from invasive pathogens through engagement of both innate and adaptive branches of the immune system. They are also likely to provide systemic protection from pathogens, by enhancing host robustness and tolerance to the invasive microbes and by inducing immune responses that prevent their growth. These properties of commensal microbiota, particularly the capacity of some bacteria to induce diverse types of antigen-specific immune responses, raises the prospect that they could be deployed as vaccine vectors to generate effective local and systemic immunity to viral and bacterial pathogens...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432128/do-the-microbiota-influence-vaccines-and-protective-immunity-to-pathogens-issues-of-sovereignty-federalism-and-points-testing-in-the-prokaryotic-and-eukaryotic-spaces-of-the-host-microbial-superorganism
#19
Andrew J Macpherson
In contrast to live attenuated vaccines, which are designed to induce immunity through a time-limited bloom in systemic tissues, the microbiota is a persistent feature of body surfaces, especially the intestine. The immune responses to the microbiota are idiosyncratic depending on the niche intimacy of different taxa and generally adapt the host to avoid overgrowth and maintain mutualism rather than to eliminate the organisms of that taxon. Both the microbiota and the host have so much molecular cross talk controlling each other, that the prokaryotic and the eukaryotic spaces of the host-microbial superorganism are federal rather than sovereign...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28431764/seasonal-monitoring-of-blue-mussel-mytilus-spp-populations-in-a-harbor-area-a-focus-on-responses-to-environmental-factors-and-chronic-contamination
#20
C Lacroix, E Duvieilbourg, N Guillou, J Guyomarch, C Bassoulet, D Moraga, G Chapalain, M Auffret
Coastal waters corresponding to macrotidal systems are among the most variable marine biotopes. Sessile animals as bivalve mollusks may however be found forming intertidal beds at high densities, as allowed by full adaptation to local conditions. A better knowledge of adaptive responses to environmental factors is required to foresee possible adverse effects of global change. At the sub-cellular level, transcriptional responses are among the earliest signals of environmental disturbances and they can reveal subtle and meaningful changes in organism exposed to stress...
April 12, 2017: Marine Environmental Research
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