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Immune system modeling

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https://www.readbyqxmd.com/read/27914084/the-zebrafish-as-a-model-for-human-bacterial-infections
#1
Melody N Neely
The development of the zebrafish (Danio rerio) infectious disease model has provided new insights and information into pathogenesis. Many of these new discoveries would not have been possible using a typical mammalian model. The advantages of using this model are many and in the last 15 years the model has been exploited for the analysis of many different pathogens. Here, we describe in detail how to perform a bacterial infection using either the adult zebrafish or zebrafish larvae using microinjection. Multiple methods of analysis are described that can be used to address specific questions pertaining to disease progression and the interactions with the immune system...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27914061/probing-oligomerized-conformations-of-defensin-in-the-membrane
#2
Wenxun Gan, Dina Schneidman, Ning Zhang, Buyong Ma, Ruth Nussinov
Computational prediction and design of membrane protein-protein interactions facilitate biomedical engineering and biotechnological applications. Due to their antimicrobial activity, human defensins play an important role in the innate immune system. Human defensins are attractive pharmaceutical targets due to their small size, broad activity spectrum, reduced immunogenicity, and resistance to proteolysis. Protein engineering based modification of defensins can improve their pharmaceutical properties. Here we present an approach to computationally probe defensins' oligomerization states in the membrane...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27913304/effects-of-nongenetic-factors-on-immune-cell-dynamics-in-early-childhood-the-generation-r-study
#3
Diana van den Heuvel, Michelle A E Jansen, Kazem Nasserinejad, Willem A Dik, Ellen G van Lochem, Liesbeth E Bakker-Jonges, Halima Bouallouch-Charif, Vincent W V Jaddoe, Herbert Hooijkaas, Jacques J M van Dongen, Henriëtte A Moll, Menno C van Zelm
BACKGROUND: . Numbers of blood leukocyte subsets are highly dynamic in childhood and differ greatly between individuals. Inter-individual variation is only partly accounted for by genetic factors. OBJECTIVE: Determine which nongenetic factors affect the dynamics of innate leukocytes, and naive and memory lymphocyte subsets. METHODS: . We performed six-color flow cytometry and linear mixed effect modeling to define the dynamics of 62 leukocyte subsets from birth to 6 years of age in 1,182 children with one to five measurements per individual...
November 29, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27913163/centralized-reminder-recall-to-increase-immunization-rates-in-young-children-how-much-bang-for-the-buck
#4
Allison Kempe, Alison W Saville, Brenda Beaty, L Miriam Dickinson, Dennis Gurfinkel, Sheri Eisert, Heather Roth, Diana Herrero, Lynn Trefren, Rachel Herlihy
OBJECTIVES: We compared effectiveness and cost-effectiveness of: 1) centralized reminder/recall (C-R/R) using the Colorado Immunization Information System (CIIS) versus practice-based reminder/recall (PB-R/R) approaches to increase immunization rates; 2) different levels of C-R/R intensity; and 3) C-R/R with versus without the name of the child's provider. METHODS: We conducted 3 sequential cluster-randomized trials involving children 19-25 months in 15 Colorado counties in 3/2013 (trial 1), 10/2013 (trial 2), and 5/2014 (trial 3)...
November 29, 2016: Academic Pediatrics
https://www.readbyqxmd.com/read/27912911/hesperidin-ameliorates-immunological-outcome-and-reduces-neuroinflammation-in-the-mouse-model-of-multiple-sclerosis
#5
Dariush Haghmorad, Mohammad Bagher Mahmoudi, Zohreh Salehipour, Zoleikha Jalayer, Amir Abbas Momtazi Brojeni, Maryam Rastin, Parviz Kokhaei, Mahmoud Mahmoudi
Multiple sclerosis (MS) is the most abundant central nervous system (CNS) inflammatory disease, which is due to the reaction of auto reactive T cells with own myelin proteins, leading to physical disorder and paralysis among people suffering the disease. Hesperidin, a flavanone glycoside found abundantly in citrus fruits possesses a wide range of pharmacological properties including potential anti-inflammatory and anti-cancer effects. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of hesperidin on MS alleviation...
November 26, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27912750/fermented-barley-and-soybean-bs-mixture-enhances-intestinal-barrier-function-in-dextran-sulfate-sodium-dss-induced-colitis-mouse-model
#6
Jong Kyu Woo, Seungho Choi, Ju-Hee Kang, Dae Eung Kim, Byung-Serk Hurh, Jong-Eun Jeon, Sun Yeou Kim, Seung Hyun Oh
BACKGROUND: Inflammatory bowel disease (IBD) is characterized by chronic or relapsing immune system activation and inflammation within the gastrointestinal tract. The lack of safety and efficacy of standard therapies, the use of food supplements for managing IBD is increasing, and many studies have reported that various food supplements provide many beneficial effects for the IBD. METHODS: This study aimed to evaluate the anti-colitis effects of dietary supplementation with a fermented barley and soybean mixture (BS) on intestinal inflammation using a murine model of IBD...
December 3, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27912060/the-hippo-pathway-kinases-lats1-2-suppress-cancer-immunity
#7
Toshiro Moroishi, Tomoko Hayashi, Wei-Wei Pan, Yu Fujita, Matthew V Holt, Jun Qin, Dennis A Carson, Kun-Liang Guan
Poorly immunogenic tumor cells evade host immunity and grow even in the presence of an intact immune system, but the complex mechanisms regulating tumor immunogenicity have not been elucidated. Here, we discovered an unexpected role of the Hippo pathway in suppressing anti-tumor immunity. We demonstrate that, in three different murine syngeneic tumor models (B16, SCC7, and 4T1), loss of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in tumor cells inhibits tumor growth. Tumor regression by LATS1/2 deletion requires adaptive immune responses, and LATS1/2 deficiency enhances tumor vaccine efficacy...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27911924/plasmodium-yoelii-nigeriensis-n67-is-a-robust-animal-model-to-study-malaria-transmission-by-south-american-anopheline-mosquitoes
#8
Alessandra S Orfano, Ana Paula M Duarte, Alvaro Molina-Cruz, Paulo F Pimenta, Carolina Barillas-Mury
Malaria is endemic in the American continent and the Amazonian rainforest is the region with the highest risk of transmission. However, the lack of suitable experimental models to infect malaria vectors from the Americas has limited the progress to understand the biology of transmission in this region. Anopheles aquasalis, a major vector in coastal areas of South America, was found to be highly refractory to infection with two strains of Plasmodium falciparum (NF54 and 7G8) and with Plasmodium berghei (mouse malaria), even when the microbiota was eliminated with antibiotics and oxidative stress was reduced with uric acid...
2016: PloS One
https://www.readbyqxmd.com/read/27911796/egr2-and-egr3-in-regulatory-t-cells-cooperatively-control-systemic-autoimmunity-through-ltbp3-mediated-tgf-%C3%AE-3-production
#9
Kaoru Morita, Tomohisa Okamura, Mariko Inoue, Toshihiko Komai, Shuzo Teruya, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Keishi Fujio
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by multiorgan inflammation induced by autoantibodies. Early growth response gene 2 (Egr2), a transcription factor essential for T-cell anergy induction, controls systemic autoimmunity in mice and humans. We have previously identified a subpopulation of CD4(+) regulatory T cells, CD4(+)CD25(-)LAG3(+) cells, that characteristically express both Egr2 and LAG3 and control mice model of lupus via TGF-β3 production. However, due to the mild phenotype of lymphocyte-specific Egr2-deficient mice, the presence of an additional regulator has been speculated...
November 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27910057/molecular-cardiac-surgery-with-recirculating-delivery-mcard-procedure-and-vector-transfer
#10
Michael G Katz, Anthony S Fargnoli, Andrew P Kendle, Charles R Bridges
Despite progress in clinical treatment, cardiovascular diseases are still the leading cause of morbidity and mortality worldwide. Therefore, novel therapeutic approaches are needed, targeting the underlying molecular mechanisms of disease with improved outcomes for patients. Gene therapy is one of the most promising fields for the development of new treatments for the advanced stages of cardiovascular diseases. The establishment of clinically relevant methods of gene transfer remains one of the principal limitations on the effectiveness of gene therapy...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909702/complement-inhibition-enables-tumor-delivery-of-lcmv-glycoprotein-pseudotyped-viruses-in-the-presence-of-antiviral-antibodies
#11
Laura Evgin, Carolina S Ilkow, Marie-Claude Bourgeois-Daigneault, Christiano Tanese de Souza, Lawton Stubbert, Michael S Huh, Victoria A Jennings, Monique Marguerie, Sergio A Acuna, Brian A Keller, Charles Lefebvre, Theresa Falls, Fabrice Le Boeuf, Rebecca A Auer, John D Lambris, J Andrea McCart, David F Stojdl, John C Bell
The systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, this strategy has not translated to other animal models. For the first time, we provide experimental evidence that antibodies generated against the lymphocytic choriomeningitis virus glycoprotein mediate robust complement-dependent viral neutralization via activation of the classical pathway...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27907104/a-new-member-of-the-growing-family-of-contact-dependent-growth-inhibition-systems-in-xenorhabdus-doucetiae
#12
Jean-Claude Ogier, Bernard Duvic, Anne Lanois, Alain Givaudan, Sophie Gaudriault
Xenorhabdus is a bacterial symbiont of entomopathogenic Steinernema nematodes and is pathogenic for insects. Its life cycle involves a stage inside the insect cadaver, in which it competes for environmental resources with microorganisms from soil and the insect gut. Xenorhabdus is, thus, a useful model for identifying new interbacterial competition systems. For the first time, in an entomopathogenic bacterium, Xenorhabdus doucetiae strain FRM16, we identified a cdi-like locus. The cdi loci encode contact-dependent inhibition (CDI) systems composed of proteins from the two-partner secretion (TPS) family...
2016: PloS One
https://www.readbyqxmd.com/read/27907005/intraluminal-flagellin-differentially-contributes-to-gut-dysbiosis-and-systemic-inflammation-following-burn-injury
#13
Logan Grimes, Allie Doyle, Aaron L Miller, Richard B Pyles, Gabor Olah, Csaba Szabo, Sarah Hoskins, Tonyia Eaves-Pyles
Burn injury is associated with a loss of gut barrier function, resulting in systemic dissemination of gut-derived bacteria and their products. The bacterial protein and TLR5 agonist, flagellin, induces non-specific innate immune responses. Because we detected flagellin in the serum of burn patients, we investigated whether gut-derived flagellin was a primary or secondary contributor to intestinal dysfunction and systemic inflammation following burn injury. The apical surface of polarized human intestinal epithelial cells (IECs), Caco-2BBe, were exposed to 50 or 500 ng of purified flagellin and 1 x 105 of an intestinal E...
2016: PloS One
https://www.readbyqxmd.com/read/27906974/in-silico-knockout-studies-of-xenophagic-capturing-of-salmonella
#14
Jennifer Scheidel, Leonie Amstein, Jörg Ackermann, Ivan Dikic, Ina Koch
The degradation of cytosol-invading pathogens by autophagy, a process known as xenophagy, is an important mechanism of the innate immune system. Inside the host, Salmonella Typhimurium invades epithelial cells and resides within a specialized intracellular compartment, the Salmonella-containing vacuole. A fraction of these bacteria does not persist inside the vacuole and enters the host cytosol. Salmonella Typhimurium that invades the host cytosol becomes a target of the autophagy machinery for degradation...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27906487/neutrophil-activation-during-acute-human-anaphylaxis-analysis-of-mpo-and-scd62l
#15
Abbie Francis, Erika Bosio, Shelley F Stone, Daniel M Fatovich, Glenn Arendts, Yusuf Nagree, Stephen P J Macdonald, Hugh Mitenko, Mani Rajee, Sally Burrows, Simon G A Brown
BACKGROUND: The mechanisms involved in the amplification of the mast cell response during anaphylaxis are unclear. Mouse models of anaphylaxis demonstrate the critical involvement of neutrophils. These innate immune cells are highly abundant in peripheral blood and can be rapidly activated to trigger both local and systemic inflammation. OBJECTIVE: To investigate neutrophil activation in peripheral blood during acute human anaphylaxis. METHODS: Patients presenting to the Emergency Department with anaphylaxis underwent blood sampling upon enrolment and at up to three subsequent time points...
December 1, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27906184/1-methyl-tryptophan-attenuates-regulatory-t-cells-differentiation-due-to-the-inhibition-of-estrogen-ido1-mrc2-axis-in-endometriosis
#16
Chunyan Wei, Jie Mei, Lingli Tang, Yukai Liu, Dajin Li, Mingqing Li, Xiaoyong Zhu
Foxp3(+) regulatory T (Treg) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal Treg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal Treg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906073/gut-barrier-structure-mucosal-immunity-and-intestinal-microbiota-in-the-pathogenesis-and-treatment-of-hiv-infection
#17
REVIEW
Camilla Tincati, Daniel C Douek, Giulia Marchetti
Over the past 10 years, extensive work has been carried out in the field of microbial translocation in HIV infection, ranging from studies on its clinical significance to investigations on its pathogenic features. In the present work, we review the most recent findings on this phenomenon, focusing on the predictive role of microbial translocation in HIV-related morbidity and mortality, the mechanisms by which it arises and potential therapeutic approaches. From a clinical perspective, current work has shown that markers of microbial translocation may be useful in predicting clinical events in untreated HIV infection, while conflicting data exist on their role in cART-experienced subjects, possibly due to the inclusion of extremely varied patient populations in cohort studies...
April 11, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27903619/interleukin-10-mediated-regenerative-postnatal-tissue-repair-is-dependent-on-regulation-of-hyaluronan-metabolism-via-fibroblast-specific-stat3-signaling
#18
Swathi Balaji, Xinyi Wang, Alice King, Louis D Le, Sukanta S Bhattacharya, Chad M Moles, Manish J Butte, Vinicio A de Jesus Perez, Kenneth W Liechty, Thomas N Wight, Timothy M Crombleholme, Paul L Bollyky, Sundeep G Keswani
The cytokine IL-10 has potent antifibrotic effects in models of adult fibrosis, but the mechanisms of action are unclear. Here, we report a novel finding that IL-10 triggers a signal transducer and activator of transcription 3 (STAT3)-dependent signaling pathway that regulates hyaluronan (HA) metabolism and drives adult fibroblasts to synthesize an HA-rich pericellular matrix, which mimics the fetal regenerative wound healing phenotype with reduced fibrosis. By using cre-lox-mediated novel, inducible, fibroblast-, keratinocyte-, and wound-specific STAT3 knockdown postnatal mice-plus syngeneic fibroblast cell-transplant models-we demonstrate that the regenerative effects of IL-10 in postnatal wounds are dependent on HA synthesis and fibroblast-specific STAT3-dependent signaling...
November 30, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27903455/complexation-hydrogels-as-potential-carriers-in-oral-vaccine-delivery-systems
#19
Mia Yoshida, Noriyasu Kamei, Keiya Muto, Jun Kunisawa, Kozo Takayama, Nicholas A Peppas, Mariko Takeda-Morishita
Most current vaccine preparations are in injectable forms, which are inconvenient to patients and ineffective in mucosal immunization. Therefore, most research in this field has been directed at developing ideal oral vaccines enabling the induction of both systemic and mucosal immune responses. In the present study, we examined the utility of a pH-responsive polymeric carrier, poly (methacrylic acid-g-ethylene glycol) [P (MAA-g-EG)] hydrogel, as a potential oral vaccine carrier that can protect cargo proteins in the gastrointestinal tract...
November 26, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27902979/altered-systemic-adipokines-in-patients-with-chronic-urticaria
#20
Hoang Kim Tu Trinh, Duy Le Pham, Ga-Young Ban, Hyun-Young Lee, Hae-Sim Park, Young-Min Ye
BACKGROUND: Increasing evidence suggests that adipokines affect immune responses and chronic urticaria (CU) is associated with an altered immune response related to chronic systemic inflammation. Our objectives were to investigate whether adipokines are involved in CU pathogenesis and to outline relationships between adipokines and urticaria severity and quality of life. METHODS: Serum adiponectin, leptin, lipocalin-2 (LCN2), interleukin (IL)-10, IL-6, and tumor necrosis factor (TNF)-α concentrations were measured by enzyme-linked immunosorbent assays in 191 CU patients and 89 healthy controls...
December 1, 2016: International Archives of Allergy and Immunology
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