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https://www.readbyqxmd.com/read/30323352/characterization-of-abscopal-effects-of-intratumoral-electroporation-mediated-il-12-gene-therapy
#1
Anandaroop Mukhopadhyay, Jocelyn Wright, Shawna Shirley, David A Canton, Christoph Burkart, Richard J Connolly, Jean S Campbell, Robert H Pierce
Intratumoral electroporation-mediated IL-12 gene therapy (IT-pIL12/EP) has been shown to be safe and effective in clinical trials, demonstrating systemic antitumor effects with local delivery of this potent cytokine. We recently optimized our IL-12 gene delivery platform to increase transgene expression and efficacy in preclinical models. Here we analyze the immunological changes induced with the new IT-pIL12/EP platform in both electroporated and distant, non-electroporated lesions. IT-pIL12/EP-treated tumors demonstrated rapid induction of IL-12-regulated pathways, as well as other cytokines and chemokines pathways, and upregulation of antigen presentation machinery...
October 15, 2018: Gene Therapy
https://www.readbyqxmd.com/read/30321239/the-cellular-phenotype-of-cytoplasmic-incompatibility-in-culex-pipiens-in-the-light-of-cidb-diversity
#2
Manon Bonneau, Frédéric Landmann, Pierrick Labbé, Fabienne Justy, Mylène Weill, Mathieu Sicard
Wolbachia are maternally inherited endosymbiotic bacteria, widespread among arthropods thanks to host reproductive manipulations that increase their prevalence into host populations. The most commonly observed manipulation is cytoplasmic incompatibility (CI). CI leads to embryonic death in crosses between i) infected males and uninfected females and ii) individuals infected with incompatible Wolbachia strains. CI can be conceptualized as a toxin-antidote system where a toxin deposited by Wolbachia in the sperm would induce embryonic death unless countered by an antidote produced by Wolbachia present in the eggs...
October 15, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/30318734/altered-expression-of-cd39-on-memory-regulatory-t-cells-in-type-1-diabetes-patients
#3
Xi Jin, Chenghui Zhang, Lina Gong, Huifang Li, Yan Wang, Qin Li, Hong Li
BACKGROUND: Type 1 diabetes (T1D) is an autoimmune disease, which is the result of autoreactive T lymphocytes attack against pancreatic islet β cells. In recent studies, regulatory T cells (Tregs) have been implicated as being part of the process in T1D. CD39 involved in suppression of inflammation, has been shown to be expressed on Tregs. However, the pathological importance of CD39 to memory Tregs population remains unclear. METHODS: We investigate subsets of Tregs with a focus on resting, effector and memory Tregs, and CD39 expression in Tregs were detected...
October 14, 2018: Journal of Diabetes
https://www.readbyqxmd.com/read/30308217/antigen-presenting-cells-and-t-lymphocytes-homing-to-the-thymus-shape-t-cell-development
#4
REVIEW
Jeremy Santamaria, Julie Darrigues, Joost P M van Meerwijk, Paola Romagnoli
Hematopoietic precursors entering the thymus undergo a maturation process leading to the generation of a variety of T cell subsets that migrate to the periphery to perform their effector functions. This maturation process is strictly regulated by multiple interactions of developing T cells with thymic stroma cells. Signals received via the T cell receptor for antigen, co-stimulatory molecules and cytokines will determine, through thymic selection and lineage choice, thymocyte-fate. Recently, different populations of peripheral antigen presenting cells and T cells have been reported to enter the thymus...
October 8, 2018: Immunology Letters
https://www.readbyqxmd.com/read/30308209/the-role-of-%C3%AE-%C3%AE-t-cells-in-spontaneous-regression-of-melanoma-tumors-in-swine
#5
Jana Cizkova, Zuzana Sinkorova, Kristyna Strnadova, Monika Cervinkova, Vratislav Horak, Jiri Sinkora, Katerina Stepanova, Marek Sinkora
Using a porcine model, we describe Melanoma-Associated CD4+ CD8hi T-lymphocytes (MATL) in peripheral blood that increase during melanoma regression. These MATL possess the CD4+ CD8hi phenotype and they have their direct counterparts in Tumor Infiltrating Lymphocytes (TIL) isolated from melanoma loci. Both MATL and CD4+ CD8hi TIL have a similar expression of selected markers indicating that they represent effector/memory αβ T-cell subset. Moreover, although TIL also contain CD4- CD8+ T-cells, only CD4+ CD8hi TIL expand during melanoma regression...
October 8, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/30308068/cd8-lymphocyte-control-of-siv-infection-during-antiretroviral-therapy
#6
Youfang Cao, Emily K Cartwright, Guido Silvestri, Alan S Perelson
CD8+ lymphocytes play an important role in suppressing in vivo viral replication in HIV infection. However, both the extent to which and the mechanisms by which CD8+ lymphocytes contribute to viral control are not completely understood. A recent experiment depleted CD8+ lymphocytes in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) on antiretroviral treatment (ART) to study the role of CD8+ lymphocytes. CD8+ lymphocytes depletion resulted in temporary plasma viremia in all studied RMs. Viral control was restored when CD8+ lymphocytes repopulated...
October 11, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/30300855/distinct-mechanisms-regulate-il1b-gene-transcription-in-lymphoid-cd4-t-cells-and-monocytes
#7
Sree H Pulugulla, Thomas A Packard, Nicole L K Galloway, Zachary W Grimmett, Gilad Doitsh, Juraj Adamik, Deborah L Galson, Warner C Greene, Philip E Auron
Interleukin 1β is a pro-inflammatory cytokine important for both normal immune responses and chronic inflammatory diseases. The regulation of the 31 kDa proIL-1β precursor coded by the IL1B gene has been extensively studied in myeloid cells, but not in lymphoid-derived CD4 T cells. Surprisingly, we found that some CD4 T cell subsets express higher levels of proIL-1β than unstimulated monocytes, despite relatively low IL1B mRNA levels. We observed a significant increase in IL1B transcription and translation in CD4 T cells upon ex vivo CD3/CD28 activation, and a similar elevation in the CCR5+ effector memory population compared to CCR5- T cells in vivo...
October 6, 2018: Cytokine
https://www.readbyqxmd.com/read/30297781/blood-meal-induced-inhibition-of-vector-borne-disease-by-transgenic-microbiota
#8
Jackie L Shane, Christina L Grogan, Caroline Cwalina, David J Lampe
Vector-borne diseases are a substantial portion of the global disease burden; one of the deadliest of these is malaria. Vector control strategies have been hindered by mosquito and pathogen resistances, and population alteration approaches using transgenic mosquitos still have many hurdles to overcome before they can be implemented in the field. Here we report a paratransgenic control strategy in which the microbiota of Anopheles stephensi was engineered to produce an antiplasmodial effector causing the mosquito to become refractory to Plasmodium berghei...
October 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/30294971/metabolic-regulation-of-innate-and-adaptive-lymphocyte-effector-responses
#9
REVIEW
Ann M Joseph, Laurel A Monticelli, Gregory F Sonnenberg
Innate and adaptive lymphocytes employ diverse effector programs that provide optimal immunity to pathogens and orchestrate tissue homeostasis, or conversely can become dysregulated to drive progression of chronic inflammatory diseases. Emerging evidence suggests that CD4+ T helper cell subsets and their innate counterparts, the innate lymphoid cell family, accomplish these complex biological roles by selectively programming their cellular metabolism in order to instruct distinct modules of lymphocyte differentiation, proliferation, and cytokine production...
November 2018: Immunological Reviews
https://www.readbyqxmd.com/read/30292618/serum-resistin-is-associated-with-impaired-endothelial-function-and-a-higher-rate-of-adverse-cardiac-events-in-patients-with-peripheral-artery-disease
#10
Joel L Ramirez, Sukaynah A Khetani, Greg J Zahner, Kimberly A Spaulding, Melinda S Schaller, Warren J Gasper, Nancy K Hills, Anne L Schafer, S Marlene Grenon
OBJECTIVE: Resistin is a hormone that has been associated with metabolic syndrome and cardiovascular disease. The role of resistin in patients with peripheral artery disease (PAD) has not been fully explored. This study seeks to understand the relationship between serum resistin, vascular function, and cardiovascular outcomes in patients with PAD. METHODS: There were 106 patients with PAD who were recruited between 2011 and 2016. Patients attended a baseline visit during which a comprehensive vascular physiology assessment including medical and surgical history, radial artery tonometry, and flow mediated-vasodilation (FMD) was completed...
October 3, 2018: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/30291285/contribution-of-spi-1-bistability-to-salmonella-enterica-cooperative-virulence-insights-from-single-cell-analysis
#11
María Antonia Sánchez-Romero, Josep Casadesús
Salmonella enterica pathogenicity island 1 (SPI-1) is a gene cluster that encodes a type III secretion system and effectors involved in epithelial cell invasion. SPI-1 undergoes bistable expression, with concomitant formation of SPI-1ON and SPI-1OFF lineages. This study describes single cell analysis of SP1-1 bistability and epithelial cell invasion, and reports the unsuspected observation that optimal invasion of epithelial cells requires the presence of both SPI-1ON and SPI-1OFF subpopulations. The contribution of SPI-1OFF cells to optimal invasion may rely on their ability to invade epithelial cells if a SPI-1ON subpopulation is present...
October 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30291273/novel-multiplex-pcr-ssp-method-for-centromeric-kir-allele-discrimination
#12
Jean-Benoît Le Luduec, Anupa Kudva, Jeanette E Boudreau, Katharine C Hsu
Allelic diversity of the KIR2DL receptors drive differential expression and ligand-binding affinities that impact natural killer cell function and patient outcomes for diverse cancers. We have developed a global intermediate resolution amplification-refractory mutation system (ARMS) PCR-SSP method for distinguishing functionally relevant subgroups of the KIR2DL receptors, as defined by phylogenetic study of the protein sequences. Use of the ARMS design makes the method reliable and usable as a kit, with all reactions utilizing the same conditions...
October 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30288750/albugo-candida-race-diversity-ploidy-and-host-associated-microbes-revealed-using-dna-sequence-capture-on-diseased-plants-in-the-field
#13
Agathe Jouet, Diane G O Saunders, Mark McMullan, Ben Ward, Oliver Furzer, Florian Jupe, Volkan Cevik, Ingo Hein, Gaetan J A Thilliez, Eric Holub, Cock van Oosterhout, Jonathan D G Jones
Physiological races of the oomycete Albugo candida are biotrophic pathogens of diverse plant species, primarily the Brassicaceae, and cause infections that suppress host immunity to other pathogens. However, A. candida race diversity and the consequences of host immunosuppression are poorly understood in the field. We report a method that enables sequencing of DNA of plant pathogens and plant-associated microbes directly from field samples (Pathogen Enrichment Sequencing: PenSeq). We apply this method to explore race diversity in A...
October 5, 2018: New Phytologist
https://www.readbyqxmd.com/read/30288743/pathogen-enrichment-sequencing-penseq-enables-population-genomic-studies-in-oomycetes
#14
Gaetan J A Thilliez, Miles R Armstrong, Tze-Yin Lim, Katie Baker, Agathe Jouet, Ben Ward, Cock van Oosterhout, Jonathan D G Jones, Edgar Huitema, Paul R J Birch, Ingo Hein
The oomycete pathogens Phytophthora infestans and P. capsici cause significant crop losses world-wide, threatening food security. In each case, pathogenicity factors, called RXLR effectors, contribute to virulence. Some RXLRs are perceived by resistance proteins to trigger host immunity, but our understanding of the demographic processes and adaptive evolution of pathogen virulence remains poor. Here, we describe PenSeq, a highly efficient enrichment sequencing approach for genes encoding pathogenicity determinants which, as shown for the infamous potato blight pathogen Phytophthora infestans, make up < 1% of the entire genome...
October 5, 2018: New Phytologist
https://www.readbyqxmd.com/read/30288359/formation-and-phenotypic-characterization-of-cd49a-cd49b-and-cd103-expressing-cd8-t-cell-populations-in-human-metastatic-melanoma
#15
Marit M Melssen, Walter Olson, Nolan A Wages, Brian J Capaldo, Ileana S Mauldin, Adela Mahmutovic, Ciara Hutchison, Cornelis J M Melief, Timothy N Bullock, Victor H Engelhard, Craig L Slingluff
Integrins α1β1 (CD49a), α2β1 (CD49b) and αEβ7 (CD103) mediate retention of lymphocytes in peripheral tissues, and their expression is upregulated on tumor infiltrating lymphocytes (TIL) compared to circulating lymphocytes. Little is known about what induces expression of these retention integrins (RI) nor whether RI define subsets in the tumor microenvironment (TME) with a specific phenotype. Human metastatic melanoma-derived CD8 TIL could be grouped into five subpopulations based on RI expression patterns: RIneg , CD49a+ only, CD49a+ CD49b+ , CD49a+ CD103+ , or positive for all three RI...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/30286211/microvesicles-from-malaria-infected-red-blood-cells-activate-natural-killer-cells-via-mda5-pathway
#16
Weijian Ye, Marvin Chew, Jue Hou, Fritz Lai, Stije J Leopold, Hooi Linn Loo, Aniruddha Ghose, Ashok K Dutta, Qingfeng Chen, Eng Eong Ooi, Nicholas J White, Arjen M Dondorp, Peter Preiser, Jianzhu Chen
Natural killer (NK) cells provide the first line of defense against malaria parasite infection. However, the molecular mechanisms through which NK cells are activated by parasites are largely unknown, so is the molecular basis underlying the variation in NK cell responses to malaria infection in the human population. Here, we compared transcriptional profiles of responding and non-responding NK cells following exposure to Plasmodium-infected red blood cells (iRBCs) and identified MDA5, a RIG-I-like receptor involved in sensing cytosolic RNAs, to be differentially expressed...
October 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/30282836/high-throughput-t-cell-receptor-sequencing-identifies-clonally-expanded-cd8-t-cell-populations-in-alopecia-areata
#17
Annemieke de Jong, Ali Jabbari, Zhenpeng Dai, Luzhou Xing, Dustin Lee, Mei Mei Li, Madeleine Duvic, Maria Hordinsky, David A Norris, Vera Price, Julian Mackay-Wiggan, Raphael Clynes, Angela M Christiano
Alopecia areata (AA) is an autoimmune disease in which cytotoxic T cells specifically target growing hair follicles. We used high-throughput TCR sequencing in the C3H/HeJ mouse model of AA and in human AA patients to gain insight into pathogenic T cell populations and their dynamics, which revealed clonal CD8+ T cell expansions in lesional skin. In the C3H/HeJ model, we observed interindividual sharing of TCRβ chain protein sequences, which strongly supports a model of antigenic drive in AA. The overlap between the lesional TCR repertoire and a population of CD8+NKG2D+ T cells in skin-draining lymph nodes identified this subset as pathogenic effectors...
October 4, 2018: JCI Insight
https://www.readbyqxmd.com/read/30276585/the-toll-pathway-in-the-central-nervous-system-of-flies-and-mammals
#18
REVIEW
Anat Shmueli, Tali Shalit, Eitan Okun, Galit Shohat-Ophir
Toll receptors, first identified to regulate embryogenesis and immune responses in the adult fly and subsequently defined as the principal sensors of infection in mammals, are increasingly appreciated for their impact on the homeostasis of the central as well as the peripheral nervous systems. Whereas in the context of immunity, the fly Toll and the mammalian TLR pathways have been researched in parallel, the expression pattern and functionality have largely been researched disparately. Herein, we provide data on the expression pattern of the Toll homologues, signaling components, and downstream effectors in ten different cell populations of the adult fly central nervous system (CNS)...
October 1, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/30267008/control-of-chronic-lymphocytic-leukemia-development-by-clonally-expanded-cd8-t-cells-that-undergo-functional-exhaustion-in-secondary-lymphoid-tissues
#19
Bola S Hanna, Philipp M Roessner, Haniyeh Yazdanparast, Dolors Colomer, Elias Campo, Sabrina Kugler, Deyan Yosifov, Stephan Stilgenbauer, Manfred Schmidt, Richard Gabriel, Peter Lichter, Martina Seiffert
Chronic lymphocytic leukemia (CLL) is associated with substantial alterations in T-cell composition and function. However, the role of T-cells in CLL remains largely controversial. Here, we utilized the Eµ-TCL1 mouse model of CLL as well as blood and lymph node samples of CLL patients to investigate the existence of anti-tumoral immune responses in CLL, and to characterize involved immune cell populations. Thereby, we identified an oligoclonal CD8+ effector T-cell population that expands along with CLL progression and controls disease development...
September 28, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/30266823/inhibition-of-mek-and-atr-is-effective-in-a-b-cell-acute-lymphoblastic-leukemia-model-driven-by-mll-af4-and-activated-ras
#20
S Haihua Chu, Evelyn J Song, Jonathan R Chabon, Janna Minehart, Chloe N Matovina, Jessica L Makofske, Elizabeth S Frank, Kenneth Ross, Richard P Koche, Zhaohui Feng, Haiming Xu, Andrei Krivtsov, Andre Nussenzweig, Scott A Armstrong
Infant B-cell acute lymphoblastic leukemias (B-ALLs) that harbor MLL-AF4 rearrangements are associated with a poor prognosis. One important obstacle to progress for this patient population is the lack of immunocompetent models that faithfully recapitulate the short latency and aggressiveness of this disease. Recent whole-genome sequencing of MLL-AF4 B-ALL samples revealed a high frequency of activating RAS mutations; however, single-agent targeting of downstream effectors of the RAS pathway in these mutated MLL- r B-ALLs has demonstrated limited and nondurable antileukemic effects...
October 9, 2018: Blood Advances
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