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Immune flux

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
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
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...
September 27, 2016: Trends in Immunology
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
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...
September 22, 2016: Fish & Shellfish Immunology
M I Ramirez, P Deolindo, I J de Messias-Reason, Emma A Arigi, H Choi, I C Almeida, I Evans-Osses
Extracellular vesicles (EVs) 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 EVs in the interaction with host cells. First, we observed that infective host cell-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
Ravi Amaravadi, Alec C Kimmelman, Eileen White
Macroautophagy (referred to here as autophagy) is induced by starvation to capture and degrade intracellular proteins and organelles in lysosomes, which recycles intracellular components to sustain metabolism and survival. Autophagy also plays a major homeostatic role in controlling protein and organelle quality and quantity. Dysfunctional autophagy contributes to many diseases. In cancer, autophagy can be neutral, tumor-suppressive, or tumor-promoting in different contexts. Large-scale genomic analysis of human cancers indicates that the loss or mutation of core autophagy genes is uncommon, whereas oncogenic events that activate autophagy and lysosomal biogenesis have been identified...
September 1, 2016: Genes & Development
Dallas B Flies, Tomoe Higuchi, Jaryse C Harris, Vibha Jha, Phyllis A Gimotty, Sarah F Adams
Although immune infiltrates in ovarian cancer are associated with improved survival, the ovarian tumor environment has been characterized as immunosuppressive, due in part to functional shifts among dendritic cells with disease progression. We hypothesized that flux in dendritic cell subpopulations with cancer progression were responsible for observed differences in antitumor immune responses in early and late-stage disease. Here we identify three dendritic cell subsets with disparate functions in the ovarian tumor environment...
August 2016: Oncoimmunology
Guoshun Wang
Phagocytes, such as neutrophils and macrophages, engulf microbes into phagosomes and launch chemical attacks to kill and degrade them. Such a critical innate immune function necessitates ion participation. Chloride, the most abundant anion in the human body, is an indispensable constituent of the myeloperoxidase (MPO)-H2 O2 -halide system that produces the potent microbicide hypochlorous acid (HOCl). It also serves as a balancing ion to set membrane potentials, optimize cytosolic and phagosomal pH, and regulate phagosomal enzymatic activities...
September 2016: Immunological Reviews
Manfred Nairz, Igor Theurl, Dominik Wolf, Günter Weiss
Iron deficiency and immune activation are the two most frequent causes of anemia, both of which are based on disturbances of iron homeostasis. Iron deficiency anemia results from a reduction of the body's iron content due to blood loss, inadequate dietary iron intake, its malabsorption, or increased iron demand. Immune activation drives a diversion of iron fluxes from the erythropoietic bone marrow, where hemoglobinization takes place, to storage sites, particularly the mononuclear phagocytes system in liver and spleen...
October 2016: Wiener Medizinische Wochenschrift
Stan de Kleijn, Gerben Ferwerda, Michelle Wiese, Jos Trentelman, Jan Cuppen, Tamas Kozicz, Linda de Jager, Peter W M Hermans, B M Lidy Verburg-van Kemenade
There is still uncertainty whether extremely low frequency electromagnetic fields (ELF-EMF) can induce health effects like immunomodulation. Despite evidence obtained in vitro, an unambiguous association has not yet been established in vivo. Here, mice were exposed to ELF-EMF for 1, 4, and 24 h/day in a short-term (1 week) and long-term (15 weeks) set-up to investigate whole body effects on the level of stress regulation and immune response. ELF-EMF signal contained multiple frequencies (20-5000 Hz) and a magnetic flux density of 10 μT...
October 2016: Bioelectromagnetics
Hendrik Koliwer-Brandl, Karl Syson, Robert van de Weerd, Govind Chandra, Ben Appelmelk, Marina Alber, Thomas R Ioerger, William R Jacobs, Jeroen Geurtsen, Stephen Bornemann, Rainer Kalscheuer
Mycobacterium tuberculosis synthesizes intra- and extracellular α-glucans that were believed to originate from separate pathways. The extracellular glucose polymer is the main constituent of the mycobacterial capsule that is thought to be involved in immune evasion and virulence. However, the role of the α-glucan capsule in pathogenesis has remained enigmatic due to an incomplete understanding of α-glucan biosynthetic pathways preventing the generation of capsule-deficient mutants. Three separate and potentially redundant pathways had been implicated in α-glucan biosynthesis in mycobacteria: the GlgC-GlgA, the Rv3032 and the TreS-Pep2-GlgE pathways...
August 2016: PLoS Pathogens
Zoë R Wallace, Sharon Sanderson, Anna Katarina Simon, Lucy Dorrell
Zidovudine (ZDV) is a widely used component of antiretroviral therapy (ART) in resource-limited settings, despite its known adverse effects, which include mitochondrial toxicity in muscle, liver and adipose tissue. It has also been associated with impaired immunological recovery. We hypothesised that ZDV might impair mitochondrial health and survival of primary T cells. We performed a cross-sectional analysis of mitochondrial function, mitophagy and susceptibility to apoptosis in healthy donor primary T cells after exposure to ZDV in vitro, together with T cells from patients who were virologically suppressed on ZDV-containing ART regimens for ≥1 year and age-matched subjects receiving non-ZDV ART regimens...
September 2016: Antiviral Research
Gustav van Niekerk, Ashwin W Isaacs, Theo Nell, Anna-Mart Engelbrecht
During an infection, expansion of immune cells, assembly of antibodies, and the induction of a febrile response collectively place continual metabolic strain on the host. These considerations also provide a rationale for nutritional support in critically ill patients. Yet, results from clinical and preclinical studies indicate that aggressive nutritional support does not always benefit patients and may occasionally be detrimental. Moreover, both vertebrates and invertebrates exhibit a decrease in appetite during an infection, indicating that such sickness-associated anorexia (SAA) is evolutionarily conserved...
2016: Mediators of Inflammation
Jonathan Braverman, Kimberly M Sogi, Daniel Benjamin, Daniel K Nomura, Sarah A Stanley
The cytokine IFN-γ coordinates macrophage activation and is essential for control of pathogens, including Mycobacterium tuberculosis However, the mechanisms by which IFN-γ controls M. tuberculosis infection are only partially understood. In this study, we show that the transcription factor hypoxia-inducible factor-1α (HIF-1α) is an essential mediator of IFN-γ-dependent control of M. tuberculosis infection both in vitro and in vivo. M. tuberculosis infection of IFN-γ-activated macrophages results in a synergistic increase in HIF-1α protein levels...
August 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Yu-Cheng Lin, Pi-Feng Chang, Hsueh-Fang Lin, Kevin Liu, Mei-Hwei Chang, Yen-Hsuan Ni
BACKGROUND & AIMS: Autophagy has been shown to be crucial in the regulation of the intracellular lipid stores in hepatocytes. We hypothesize that immunity-related GTPase family M (IRGM) gene (an autophagy-related gene) variants confer the susceptibility to nonalcoholic fatty liver disease (NAFLD) development. METHODS: 832 obese children and adolescents aged 6-18 years were recruited. NAFLD was determined by liver ultrasonography. We genotyped PNPLA3 rs738409, GCKR rs780094, TM6SF2rs58542926, sixIRGM single nucleotide polymorphisms (rs13361189, rs9637876, rs72553867, rs10065172, rs1000113, and rs11747270)...
July 11, 2016: Journal of Hepatology
I Oancea, R Movva, I Das, D Aguirre de Cárcer, V Schreiber, Y Yang, A Purdon, B Harrington, M Proctor, R Wang, Y Sheng, M Lobb, R Lourie, P Ó Cuív, J A Duley, J Begun, T H J Florin
OBJECTIVE: Mercaptopurine (MP) and pro-drug azathioprine are 'first-line' oral therapies for maintaining remission in IBD. It is believed that their pharmacodynamic action is due to a slow cumulative decrease in activated lymphocytes homing to inflamed gut. We examined the role of host metabolism, lymphocytes and microbiome for the amelioration of colitis by the related thioguanine (TG). DESIGN: C57Bl/6 mice with or without specific genes altered to elucidate mechanisms responsible for TG's actions were treated daily with oral or intrarectal TG, MP or water...
July 13, 2016: Gut
L Xing
Background: The study of the effect of different dialysis methods on cellular immune function of maintenance haemodialysis (MHD) patients should provide theoretical support for deciding on the best method of blood purification that effectively improves cellular immune function of haemodialysis patients. Subjects and Method: Sixty MHD patients were randomly divided into three groups that respectively received treatment of haemodialysis (HD), high flux haemodialysis (HFHD) and haemodiafiltration (HDF)...
April 18, 2016: West Indian Medical Journal
Balu K Chacko, Stephanie B Wall, Philip A Kramer, Saranya Ravi, Tanecia Mitchell, Michelle S Johnson, Landon Wilson, Stephen Barnes, Aimee Landar, Victor M Darley-Usmar
Metabolic control of cellular function is significant in the context of inflammation-induced metabolic dysregulation in immune cells. Generation of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide are one of the critical events that modulate the immune response in neutrophils. When activated, neutrophil NADPH oxidases consume large quantities of oxygen to rapidly generate ROS, a process that is referred to as the oxidative burst. These ROS are required for the efficient removal of phagocytized cellular debris and pathogens...
June 23, 2016: Redox Biology
Melanie Verena Paul, Srignanakshi Iyer, Carmen Amerhauser, Martin Lehmann, Joost T van Dongen, Peter Geigenberger
Subgroup-VII-ethylene-response-factor (ERF-VII) transcription factors are involved in the regulation of hypoxic gene expression and regulated by proteasome-mediated proteolysis via the oxygen-dependent branch of the N-end-rule pathway. While research into ERF-VII mainly focused on their role to regulate anoxic gene expression, little is known on the impact of this oxygen-sensing system in regulating plant metabolism and growth. By comparing Arabidopsis (Arabidopsis thaliana) plants overexpressing N-end-rule-sensitive and insensitive forms of the ERF-VII-factor RAP2...
September 2016: Plant Physiology
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