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Immune flux

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https://www.readbyqxmd.com/read/28057386/nanoparticles-decorated-with-viral-antigens-are-more-immunogenic-at-low-surface-density
#1
Matthew G Brewer, Anthony DiPiazza, Joshua Acklin, Changyong Feng, Andrea J Sant, Stephen Dewhurst
There is an urgent need to develop protective vaccines for high priority viral pathogens. One approach known to enhance immune responses to viral proteins is to display them on a nanoparticle (NP) scaffold. However, little is known about the effect of protein density on the B cell response to antigens displayed on NPs. To address this question HIV-1 Envelope (Env) and influenza hemagglutinin (HA) were displayed on a polystyrene-based NP scaffold at various densities - corresponding to mean antigen distances that span the range encountered on naturally occurring virions...
February 1, 2017: Vaccine
https://www.readbyqxmd.com/read/28056107/autophagy-is-an-innate-mechanism-associated-with-leprosy-polarization
#2
Bruno Jorge de Andrade Silva, Mayara Garcia de Mattos Barbosa, Priscila Ribeiro Andrade, Helen Ferreira, José Augusto da Costa Nery, Suzana Côrte-Real, Gilberto Marcelo Sperandio da Silva, Patricia Sammarco Rosa, Mario Fabri, Euzenir Nunes Sarno, Roberta Olmo Pinheiro
Leprosy is a chronic infectious disease that may present different clinical forms according to the immune response of the host. Levels of IFN-γ are significantly raised in paucibacillary tuberculoid (T-lep) when compared with multibacillary lepromatous (L-lep) patients. IFN-γ primes macrophages for inflammatory activation and induces the autophagy antimicrobial mechanism. The involvement of autophagy in the immune response against Mycobacterium leprae remains unexplored. Here, we demonstrated by different autophagic assays that LC3-positive autophagosomes were predominantly observed in T-lep when compared with L-lep lesions and skin-derived macrophages...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28012149/endoplasmic-reticulum-stress-and-apoptosis-triggered-by-sub-chronic-lead-exposure-in-mice-spleen-a-histopathological-study
#3
Giovanni Corsetti, Claudia Romano, Alessandra Stacchiotti, Evasio Pasini, Francesco S Dioguardi
Lead (Pb) is an environmental oncogenic metal that induces immunotoxicity and anaemia. Emerging evidence has linked Pb toxicity with endoplasmic reticulum-driven apoptosis and autophagy. Glucose-regulated protein of 78 kDa (Grp78 or binding immunoglobulin protein (BiP)), a master endoplasmic reticulum chaperone, drives macrophage activation and regulates protein folding and calcium flux in response to heavy metals. The spleen may be involved in Pb poisoning due to its crucial role in erythrocatheresis and immune response, although there are no data to support this theory...
December 24, 2016: Biological Trace Element Research
https://www.readbyqxmd.com/read/28008941/systemic-wound-healing-associated-with-local-sub-cutaneous-mechanical-stimulation
#4
Christine Nardini, Valentina Devescovi, Yuanhua Liu, Xiaoyuan Zhou, Youtao Lu, Jennifer E Dent
Degeneration is a hallmark of autoimmune diseases, whose incidence grows worldwide. Current therapies attempt to control the immune response to limit degeneration, commonly promoting immunodepression. Differently, mechanical stimulation is known to trigger healing (regeneration) and it has recently been proposed locally for its therapeutic potential on severely injured areas. As the early stages of healing consist of altered intra- and inter-cellular fluxes of soluble molecules, we explored the potential of this early signal to spread, over time, beyond the stimulation district and become systemic, to impact on distributed or otherwise unreachable injured areas...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28007431/quantifying-in-vivo-murine-antigen-specific-t-cell-responses-without-requirement-for-prior-knowledge-of-antigen-identity
#5
Nour Kibbi, Enping Hong, Harib Ezaldein, Douglas Hanlon, Tarek Fahmy, Richard Edelson
Extracorporeal Photochemotherapy (ECP) is a widely applied anti-cancer immunotherapy for patients with cutaneous T cell lymphoma (CTCL). By using apoptotic malignant cells as a source of patient-specific tumor antigen, it enables clinically relevant and curative anti-CTCL immunity, with potential efficacy in other tumors. Currentmethods to track patient-specific responses are tedious, and new methods are needed to assess putative global immunity. We developed a clinically practical method to assess antigen-specific T cell activation that does not rely on knowledge of the particular antigen, thereby eliminating the requirement for patient-specific reagents...
November 30, 2016: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28005419/aging-of-the-immune-system-mechanisms-and-therapeutic-targets
#6
Cornelia M Weyand, Jörg J Goronzy
Beginning with the sixth decade of life, the human immune system undergoes dramatic aging-related changes, which continuously progress to a state of immunosenescence. The aging immune system loses the ability to protect against infections and cancer and fails to support appropriate wound healing. Vaccine responses are typically impaired in older individuals. Conversely, inflammatory responses mediated by the innate immune system gain in intensity and duration, rendering older individuals susceptible to tissue-damaging immunity and inflammatory disease...
December 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27974195/human-stem-cell-like-memory-t-cells-are-maintained-in-a-state-of-dynamic-flux
#7
Raya Ahmed, Laureline Roger, Pedro Costa Del Amo, Kelly L Miners, Rhiannon E Jones, Lies Boelen, Tinhinane Fali, Marjet Elemans, Yan Zhang, Victor Appay, Duncan M Baird, Becca Asquith, David A Price, Derek C Macallan, Kristin Ladell
Adaptive immunity requires the generation of memory T cells from naive precursors selected in the thymus. The key intermediaries in this process are stem cell-like memory T (TSCM) cells, multipotent progenitors that can both self-renew and replenish more differentiated subsets of memory T cells. In theory, antigen specificity within the TSCM pool may be imprinted statically as a function of largely dormant cells and/or retained dynamically by more transitory subpopulations. To explore the origins of immunological memory, we measured the turnover of TSCM cells in vivo using stable isotope labeling with heavy water...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27911401/an-optimized-protocol-to-analyze-glycolysis-and-mitochondrial-respiration-in-lymphocytes
#8
Javier Traba, Pietro Miozzo, Billur Akkaya, Susan K Pierce, Munir Akkaya
Lymphocytes respond to a variety of stimuli by activating intracellular signaling pathways, which in turn leads to rapid cellular proliferation, migration and differentiation, and cytokine production. All of these events are tightly linked to the energy status of the cell, and therefore studying the energy-producing pathways may give clues about the overall functionality of these cells. The extracellular flux analyzer is a commonly used device for evaluating the performance of glycolysis and mitochondrial respiration in many cell types...
November 21, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27900586/role-of-prolactin-in-promotion-of-immune-cell-migration-into-the-mammary-gland
#9
Riva Dill, Ameae M Walker
Immune cells in the mammary gland play a number of important roles, including protection against infection during lactation and, after passing into milk, modulation of offspring immunity. However, little is known about the mechanism of recruitment of immune cells to the lactating gland in the absence of infection. Given the importance of prolactin to other aspects of lactation, we hypothesized it would also play a role in immune cell recruitment. Prolactin treatment of adult female mice for a period equivalent to pregnancy and the first week of lactation increased immune cell flux through the mammary gland, as reflected in the number of immune cells in mammary gland-draining, but not other lymph nodes...
November 29, 2016: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/27896219/enhanced-therapeutic-efficacy-in-cancer-patients-by-short-term-fasting-the-autophagy-connection
#10
REVIEW
Gustav van Niekerk, Suzèl M Hattingh, Anna-Mart Engelbrecht
Preclinical studies suggest that fasting prior to chemotherapy may be an effective strategy to protect patients against the adverse effects of chemo-toxicity. Fasting may also sensitize cancer cells to chemotherapy. It is further suggested that fasting may similarly augment the efficacy of oncolytic viral therapy. The primary mechanism mediating these beneficial effects is thought to relate to the fact that fasting results in a decrease of circulating growth factors. In turn, such fasting cues would prompt normal cells to redirect energy toward cell maintenance and repair processes, rather than growth and proliferation...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27883961/molecular-visualizing-and-quantifying-immune-associated-peroxynitrite-fluxes-in-phagocytes-and-mouse-inflammation-model
#11
Zan Li, Shi-Hai Yan, Chen Chen, Zhi-Rong Geng, Jia-Yin Chang, Chun-Xia Chen, Bing-Huan Huang, Zhi-Lin Wang
Reactions of peroxynitrite (ONOO(-)) with biomolecules can lead to cytotoxic and cytoprotective events. Due to the difficulty of directly and unambiguously measuring its levels, most of the beneficial effects associated with ONOO(-) in vivo remain controversial or poorly characterized. Recently, optical imaging has served as a powerful noninvasive approach to studying ONOO(-) in living systems. However, ratiometric probes for ONOO(-) are currently lacking. Herein, we report the design, synthesis, and biological evaluation of F482, a novel fluorescence indicator that relies on ONOO(-)-induced diene oxidation...
April 15, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27827303/an-hdac6-inhibitor-confers-protection-and-selectively-inhibits-b-cell-infiltration-in-dss-induced-colitis-in-mice
#12
Anh Do, Robert C Reid, Rink-Jan Lohman, Matthew J Sweet, David P Fairlie, Abishek Iyer
Small molecule histone deacetylase (HDAC) inhibitors with anti-inflammatory activity may be candidates for targeting intestinal inflammatory pathways in inflammatory bowel disease (IBD). This study investigated whether treatment with a potent HDAC6 inhibitor, BML-281, could protect against colonic inflammation and prevent inflammatory cell infiltration into the colon to drive disease pathology in a mouse model of acute dextran sodium sulfate (DSS) colitis. Control and acute DSS-colitis mice were treated with BML-281 (1 mg/kg per day s...
January 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27815390/kv1-3-channels-mark-functionally-competent-cd8-tumor-infiltrating-lymphocytes-in-head-and-neck-cancer
#13
Ameet A Chimote, Peter Hajdu, Alexandros M Sfyris, Brittany N Gleich, Trisha Wise-Draper, Keith A Casper, Laura Conforti
Tumor-infiltrating lymphocytes (TIL) are potent mediators of an antitumor response. However, their function is attenuated in solid tumors. CD8(+) T-cell effector functions, such as cytokine and granzyme production, depend on cytoplasmic Ca(2+), which is controlled by ion channels. In particular, Kv1.3 channels regulate the membrane potential and Ca(2+) influx in human effector memory T (TEM) cells. In this study, we assessed the contribution of reduced Kv1.3 and Ca(2+) flux on TIL effector function in head and neck cancer (HNC)...
January 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/27780657/metabolic-reprogramming-inflammation-fuelling-the-host-response-to-pathogens
#14
REVIEW
Laura E Gleeson, Frederick J Sheedy
Successful immune responses to pathogens rely on efficient host innate processes to contain and limit bacterial growth, induce inflammatory response and promote antigen presentation for the development of adaptive immunity. This energy intensive process is regulated through multiple mechanisms including receptor-mediated signaling, control of phago-lysomal fusion events and promotion of bactericidal activities. Inherent macrophage activities therefore are dynamic and are modulated by signals and changes in the environment during infection...
October 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/27703191/measuring-populations-to-improve-vaccination-coverage
#15
Nita Bharti, Ali Djibo, Andrew J Tatem, Bryan T Grenfell, Matthew J Ferrari
In low-income settings, vaccination campaigns supplement routine immunization but often fail to achieve coverage goals due to uncertainty about target population size and distribution. Accurate, updated estimates of target populations are rare but critical; short-term fluctuations can greatly impact population size and susceptibility. We use satellite imagery to quantify population fluctuations and the coverage achieved by a measles outbreak response vaccination campaign in urban Niger and compare campaign estimates to measurements from a post-campaign survey...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27698456/microbial-degradation-of-cellular-kinases-impairs-innate-immune-signaling-and-paracrine-tnf%C3%AE-responses
#16
Kenneth Barth, Caroline Attardo Genco
The NFκB and MAPK signaling pathways are critical components of innate immunity that orchestrate appropriate immune responses to control and eradicate pathogens. Their activation results in the induction of proinflammatory mediators, such as TNFα a potent bioactive molecule commonly secreted by recruited inflammatory cells, allowing for paracrine signaling at the site of an infection. In this study we identified a novel mechanism by which the opportunistic pathogen Porphyromonas gingivalis dampens innate immune responses by disruption of kinase signaling and degradation of inflammatory mediators...
October 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27692616/the-intracellular-cholesterol-landscape-dynamic-integrator-of-the-immune-response
#17
REVIEW
Michael B Fessler
Cholesterol has typically been considered an exogenous, disease-related factor in immunity; however, recent literature suggests that a paradigm shift is in order. Sterols are now recognized to ligate several immune receptors. Altered flux through the mevalonic acid synthesis pathway also appears to be a required event in the antiviral interferon (IFN) response of macrophages and in the activation, proliferation, and differentiation of T cells. In this review, evidence is discussed that suggests an intrinsic, 'professional' role for sterols and oxysterols in macrophage and T-cell immunity...
December 2016: Trends in Immunology
https://www.readbyqxmd.com/read/27689012/inhibition-of-ror%C3%AE-%C3%AE-suppresses-atherosclerosis-via-inhibition-of-both-cholesterol-absorption-and-inflammation
#18
Cyrielle Billon, Sadichha Sitaula, Thomas P Burris
OBJECTIVE: Cardiovascular diseases (CVDs) are the leading cause of mortality in Western countries. Atherosclerosis is a multi-step inflammatory disease characterized at early stages by accumulation of cholesterol in the arterial wall followed by recruitment of immune cells. We sought to determine if pharmacological suppression of RORα/γ activity is beneficial in treatment of atherosclerosis. METHODS: To identify the role of RORα and RORγ in atherosclerosis, we used the LDL-R(-/-) mouse model of atherosclerosis placed on a high cholesterol diet treated with SR1001, a RORα/γ inverse agonist, for four weeks...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27666190/salmonella-spv-locus-suppresses-host-innate-immune-responses-to-bacterial-infection
#19
Shu-Yan Wu, Li-Dan Wang, Jin-Ling Li, Guang-Mei Xu, Mei-Ling He, Yuan-Yuan Li, Rui Huang
Salmonella enterica serovar typhimurium (S. typhimurium) is globally distributed and causes massive morbidity and mortality in humans and animals. S. typhimurium carries Salmonella plasmid virulence (spv) locus, which is highly conserved and closely related to bacterial pathogenicity, while its exact role in host immune responses during infection remains to be elucidated. To counteract the invaders, the host has evolved numerous strategies, among which the innate immunity and autophagy act as the first defense...
November 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27665486/dynamic-flux-of-microvesicles-modulate-parasite-host-cell-interaction-of-trypanosoma-cruzi-in-eukaryotic-cells
#20
M I Ramirez, P Deolindo, I J de Messias-Reason, Emma A Arigi, H Choi, I C Almeida, I Evans-Osses
Extracellular vesicles released from pathogens may alter host cell functions. We previously demonstrated the involvement of host cell-derived microvesicles (MVs) during early interaction between Trypanosoma cruzi metacyclic trypomastigote (META) stage and THP-1 cells. Here, we aim to understand the contribution of different parasite stages and their extracellular vesicles in the interaction with host cells. First, we observed that infective host cell-derived trypomastigote (tissue culture-derived trypomastigote [TCT]), META, and noninfective epimastigote (EPI) stages were able to induce different levels of MV release from THP-1 cells; however, only META and TCT could increase host cell invasion...
September 25, 2016: Cellular Microbiology
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