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Innate Immunity

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https://www.readbyqxmd.com/read/27932520/myeloid-derived-nf-%C3%AE%C2%BAb-negative-regulation-of-pu-1-and-c-ebp-%C3%AE-driven-pro-inflammatory-cytokine-production-restrains-lps-induced-shock
#1
Simone Vanoni, Yi-Ting Tsai, Amanda Waddell, Lisa Waggoner, Jared Klarquist, Senad Divanovic, Kasper Hoebe, Kris A Steinbrecher, Simon P Hogan
Sepsis is a life-threatening event predominantly caused by Gram-negative bacteria. Bacterial infection causes a pronounced macrophage (MΦ) and dendritic cell activation that leads to excessive pro-inflammatory cytokine IL-1β, IL-6 and TNF-α production (cytokine storm), resulting in endotoxic shock. Previous experimental studies have revealed that inhibiting NF-κB signaling ameliorates disease symptoms; however, the contribution of myeloid p65 in endotoxic shock remains elusive. In this study, we demonstrate increased mortality in mice lacking p65 in the myeloid lineage (p65(Δmye)) compared with wild type mice upon ultra-pure LPS challenge...
December 8, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27913794/tlr-ligands-but-not-modulators-of-histone-modifiers-can-induce-the-complex-immune-response-pattern-of-endotoxin-tolerance-in-mammary-epithelial-cells
#2
Juliane Günther, Wolfram Petzl, Holm Zerbe, Hans-Joachim Schuberth, Hans-Martin Seyfert
Excessive stimulation of the TLR4 axis through LPS reduces the expression of some cytokine genes in immune cells, while stimulating the expression of immune defense genes during a subsequent bacterial infection. This endotoxin tolerance (ET) is mediated via epigenetic mechanisms. Priming the udder of cows with LPS was shown to induce ET in mammary epithelial cells (MEC), thereby protecting the udder against reinfection for some time. Seeking alternatives to LPS priming we tried to elicit ET by priming MEC with either lipopeptide (Pam2CSK4) via the TLR2/6 axis or inhibitors of histone-modifying enzymes...
December 1, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27913793/inflammatory-signaling-pathways-induced-by-helicobacter-pylori-in-primary-human-gastric-epithelial-cells
#3
Cong Tri Tran, Magali Garcia, Martine Garnier, Christophe Burucoa, Charles Bodet
Inflammatory signaling pathways induced by Helicobacter pylori remain unclear, having been studied mostly on cell-line models derived from gastric adenocarcinoma with potentially altered signaling pathways and nonfunctional receptors. Here, H. pylori-induced signaling pathways were investigated in primary human gastric epithelial cells. Inflammatory response was analyzed on chemokine mRNA expression and production after infection of gastric epithelial cells by H. pylori strains, B128 and B128ΔcagM, a cag type IV secretion system defective strain...
December 1, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27913792/genetic-engineering-approach-to-develop-next-generation-reagents-for-endotoxin-quantification
#4
Hikaru Mizumura, Norihiko Ogura, Jun Aketagawa, Maki Aizawa, Yuki Kobayashi, Shun-Ichiro Kawabata, Toshio Oda
The bacterial endotoxin test, which uses amebocyte lysate reagents of horseshoe crab origin, is a sensitive, reproducible and simple assay to measure endotoxin concentration. To develop sustainable raw materials for lysate reagents that do not require horseshoe crabs, three recombinant protease zymogens (factor C, derived from mammalian cells; factor B; and the proclotting enzyme derived from insect cells) were prepared using a genetic engineering technique. Recombinant cascade reagents (RCRs) were then prepared to reconstruct the reaction cascade in the amebocyte lysate reagent...
December 1, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27913791/circadian-transcription-factor-bmal1-regulates-innate-immunity-against-select-rna-viruses
#5
Tanmay Majumdar, Jayeeta Dhar, Sonal Patel, Roman Kondratov, Sailen Barik
BMAL1 (brain and muscle ARNT-like protein 1, also known as MOP3 or ARNT3) belongs to the family of the basic helix-loop-helix (bHLH)-PAS domain-containing transcription factors, and is a key component of the molecular oscillator that generates circadian rhythms. Here, we report that BMAL1-deficient cells are significantly more susceptible to infection by two major respiratory viruses of the Paramyxoviridae family, namely RSV and PIV3. Embryonic fibroblasts from Bmal1(-/-) mice produced nearly 10-fold more progeny virus than their wild type controls...
December 1, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27884946/analysis-of-the-caenorhabditis-elegans-innate-immune-response-to-coxiella-burnetii
#6
James M Battisti, Lance A Watson, Myo T Naung, Adam M Drobish, Ekaterina Voronina, Michael F Minnick
The nematode Caenorhabditis elegans is well established as a system for characterization and discovery of molecular mechanisms mediating microbe-specific inducible innate immune responses to human pathogens. Coxiella burnetii is an obligate intracellular bacterium that causes a flu-like syndrome in humans (Q fever), as well as abortions in domesticated livestock, worldwide. Initially, when wild type C. elegans (N2 strain) was exposed to mCherry-expressing C. burnetii (CCB) a number of overt pathological manifestations resulted, including intestinal distension, deformed anal region and a decreased lifespan...
November 24, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27879415/the-angiotensin-converting-enzyme-inhibitor-captopril-rescues-mice-from-endotoxin-induced-lethal-hepatitis
#7
Pu Ge, Rong Jiang, Xin Yao, Jing Li, Jie Dai, Li Zhang, Bin Ye
The renin-angiotensin system is classically regarded as a crucial regulator of circulatory homeostasis, but recent studies also revealed its pro-inflammatory roles. The beneficial effects of the angiotensin-converting enzyme inhibitor (ACEI) in severe inflammatory injury in the lung and heart have been previously reported, but its potential effects on lethal hepatitis were unknown. In this study, a mouse model with LPS/d-galactosamine (GalN)-induced fulminant hepatitis were used to test the protective potential of captopril, a representative ACEI...
November 22, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27872382/in-utero-exposure-to-lps-alters-the-postnatal-acute-phase-response-in-beef-heifers
#8
Jeffery A Carroll, Nicole C Burdick Sanchez, John D Arthingon, Corwin D Nelson, Aimee L Benjamin, Filiz T Korkmaz, David E Kerr, Phillip A Lancaster
The potential effect of prenatal LPS exposure on the postnatal acute phase response (APR) to an LPS challenge in heifers was determined. Pregnant crossbred cows were separated into prenatal immune stimulation (PIS) and saline groups (Control). From these treatments, heifer calves were identified at weaning to subsequently receive an exogenous LPS challenge. Sickness behavior scores (SBS) were recorded and blood samples were collected at 30-min intervals from -2 to 8 h and again at 24 h relative to the LPS challenge...
November 21, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27864558/prospective-study-of-the-innate-cellular-immune-response-in-low-vaccine-responder-children
#9
Naveen Surendran, Ted Nicolosi, Ravinder Kaur, Matthew Morris, Michael Pichichero
We recently reported our findings from a longitudinal, prospective study where we identified 10% infants who were low vaccine responders (LVR) at age 9-12 mo following routine primary series vaccine schedule. We found multiple cellular deficiencies in LVR children, including low number of memory B cells, reduced polyclonal stimulation of naïve/memory T cell response and suboptimal APC response. These children outgrew their poor vaccine response by the time they received booster doses of vaccine. Studies in human infant innate immunity are rare because of the unique challenges in specimen collection...
November 18, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27856789/collectins-h-ficolin-and-ll-37-reduce-influence-viral-replication-in-human-monocytes-and-modulate-virus-induced-cytokine-production
#10
Mitchell R White, Shweta Tripathi, Anamika Verma, Paul Kingma, Kazue Takahashi, Jens Jensenius, Steffen Thiel, Guangshun Wang, Erika C Crouch, Kevan L Hartshorn
Infiltrating activated monocytes are important mediators of damaging inflammation during influenza A virus (IAV) infection. We show that soluble respiratory proteins [collectins, surfactant proteins D (SP-D) and mannose binding lectin (MBL), H-ficolin and LL-37] inhibit replication of seasonal IAV in human monocytes. The collectins and H-ficolin also increased viral uptake by the cells, while LL-37 did not. H-ficolin was able to inhibit replication of the 2009 pandemic H1N1 strain (Cal09) in monocytes, but SP-D and LL-37 had significantly fewer inhibitory effects on this strain than on seasonal IAV...
November 17, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27821649/zinc-supplementation-leads-to-immune-modulation-and-improved-survival-in-a-juvenile-model-of-murine-sepsis
#11
Hammad A Ganatra, Brian M Varisco, Kelli Harmon, Patrick Lahni, Amy Opoka, Hector R Wong
Children with severe sepsis are known to have altered zinc homeostasis and decreased circulating zinc levels, suggesting a role for zinc supplementation to improve outcomes. We tested the hypothesis that zinc supplementation would improve survival in a juvenile model of polymicrobial sepsis. Juvenile (13-14-d-old) C57BL/6 mice were treated with 10 mg/kg of zinc via i.p. injections (or vehicle) for 3 d prior to induction of polymicrobial sepsis via i.p. cecal slurry injections. Survival after sepsis was followed for 3 d, and bacterial clearance, ex vivo phagocytosis, systemic inflammatory markers and neutrophil extracellular trap (NET) formation were quantified...
November 7, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27821648/novel-augmentation-by-bufalin-of-protein-kinase-c-induced-cyclooxygenase-2-and-il-8-production-in-human-breast-cancer-cells
#12
Hsiao-Ting Chen, David Sun, Yen-Chun Peng, Pu-Hong Kao, Yuh-Lin Wu
Cyclooxygenase-2 (COX-2) and IL-8 are two inflammatory mediators induced by protein kinase C (PKC) via various stimuli. Both contribute significantly to cancer progression. Bufalin, a major active component of the traditional Chinese medicine Chan Su, is known to induce apoptosis in various cancer cells. This study clarifies the role and mechanism of bufalin action during PKC regulation of COX-2/IL-8 expression and investigates the associated impact on breast cancer. Using MB-231 breast cancer cells, bufalin augments PKC induction of COX-2/IL-8 at both the protein and mRNA levels, and the production of prostaglandin E2 (PGE2) and IL-8...
November 7, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27821647/preclinical-evaluation-of-drugs-to-block-inflammation-driven-preterm-birth
#13
Demelza J Ireland, Elizabeth A Nathan, Shaofu Li, Adrian K Charles, Lisa F Stinson, Matthew W Kemp, John P Newnham, Jeffrey A Keelan
Intrauterine inflammation, the major cause of early preterm birth, can have microbial and sterile aetiologies. We assessed in a Transwell model the anti-inflammatory efficacies of five drugs on human extraplacental membranes delivered after preterm spontaneous labour (30-34 wk). Drugs [TPCA1 (IKKβ inhibitor), 5 z-7-oxozeaenol (OxZ, TAK1 inhibitor), inhibitor of NF-κB essential modulator binding domain (iNBD), SB239063 (p38 MAPK inhibitor) and N-acetyl cysteine (free radical scavenger free radicals)] were added after 12 h equilibration to the amniotic compartment...
November 7, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27794069/new-il-15-receptor-%C3%AE-splicing-variants-identified-in-intestinal-epithelial-caco-2-cells
#14
Celia Escudero-Hernández, Beatriz Martínez-Abad, Violeta Ruipérez, José A Garrote, Eduardo Arranz
IL-15 is a pleiotropic cytokine related to IL-2 which acts at a broader level than its counterpart. It is presented through its specific high-affinity receptor, IL-15Rα. Both cytokine and receptor are tightly regulated at multiple levels and are widely distributed. Thus, deregulation of their expression leads to an inflammatory immune response. Variants of splicing of IL-15Rα have been described in immune and barrier cells; however, their presence has not been focused on intestinal epithelial cells. In this study, we describe five new alternative variants of splicing of IL-15Rα in Caco-2 cells...
October 28, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27794068/c4b-binding-protein-negatively-regulates-tlr1-2-response
#15
Naoko Morita, Ikuko Yamai, Koichiro Takahashi, Yutaka Kusumoto, Takuma Shibata, Toshihiko Kobayashi, Mayumi I Nonaka, Isao Ichimonji, Hidekazu Takagi, Kensuke Miyake, Sachiko A Takamura
TLR2 associates with TLR1 and recognizes microbial lipoproteins. Pam3CSK4, a triacylated lipoprotein, is anchored to the extracellular domain of TLR1 and TLR2 and induces pro-inflammatory signals. Here we show that C4b binding protein (C4BP), which is a complement pathway inhibitor, is a TLR2-associated molecule. Immunoprecipitation assay using anti-TLR2 mAb shows that C4BP binds to TLR2. In C4BP-deficient mice, Pam3CSK4-induced IL-6 levels were increased compared with wild type mice. In C4BP-expressing cells, Pam3CSK4-induced IL-8 production was reduced depending on the C4BP expression levels...
October 28, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27697850/environment-impacts-innate-immune-ontogeny
#16
Mathieu Garand, Bing Cai, Tobias R Kollmann
Susceptibility to infection and response to vaccination differ between populations and as a function of age. The underlying mechanisms for this age- and population-dependent variation are not known. Specifically, it is unclear if these variations are due to differences in genetically encoded host programs or driven by environmental influences or a combination of both. To address the relationship between gene and environment regarding immune ontogeny, we determined the innate cytokine responses following PRR stimulation of blood mononuclear cells at birth, 1, and 2 yr of age in infants from Caucasian vs...
October 3, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27694635/muramyl-peptides-activate-innate-immunity-conjointly-via-yb1-and-nod2
#17
Alexander G Laman, Richard Lathe, Anna O Shepelyakovskaya, Alexandra Gartseva, Feodor A Brovko, Svetlana Guryanova, Ludmila Alekseeva, Elena A Meshcheryakova, Vadim T Ivanov
Bacterial cell wall muramyl dipeptide (MDP) and glucosaminyl-MDP (GMDP) are potent activators of innate immunity. Two receptor targets, NOD2 and YB1, have been reported; we investigated potential overlap of NOD2 and YB1 pathways. Separate knockdown of NOD2 and YB1 demonstrates that both contribute to GMDP induction of NF-κB expression, a marker of innate immunity, although excess YB1 led to induction in the absence of NOD2. YB1 and NOD2 co-migrated on sucrose gradient centrifugation, and GMDP addition led to the formation of higher molecular mass complexes containing both YB1 and NOD2...
September 30, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27688705/lps-induced-expression-of-cd14-in-the-trif-pathway-is-epigenetically-regulated-by-sulforaphane-in-porcine-pulmonary-alveolar-macrophages
#18
Qin Yang, Maren J Pröll, Dessie Salilew-Wondim, Rui Zhang, Dawit Tesfaye, Huitao Fan, Mehmet U Cinar, Christine Große-Brinkhaus, Ernst Tholen, Mohammad A Islam, Michael Hölker, Karl Schellander, Muhammad J Uddin, Christiane Neuhoff
Pulmonary alveolar macrophages (AMs) are important in defense against bacterial lung inflammation. Cluster of differentiation 14 (CD14) is involved in recognizing bacterial lipopolysaccharide (LPS) through MyD88-dependent and TRIF pathways of innate immunity. Sulforaphane (SFN) shows anti-inflammatory activity and suppresses DNA methylation. To identify CD14 epigenetic changes by SFN in the LPS-induced TRIF pathway, an AMs model was investigated in vitro CD14 gene expression was induced by 5 µg/ml LPS at the time point of 12 h and suppressed by 5 µM SFN...
September 29, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27670946/autophagy-is-induced-by-anti-neutrophil-cytoplasmic-abs-and-promotes-neutrophil-extracellular-traps-formation
#19
Li-Li Sha, Huan Wang, Chen Wang, Hong-Ying Peng, Min Chen, Ming-Hui Zhao
Dysregulated neutrophil extracellular traps (NETs) formation contributes to the pathogenesis of anti-neutrophil cytoplasmic Ab (ANCA)-associated vasculitis (AAV). Increasing evidence indicates that autophagy is involved in the process of NETs formation. In this study, we aimed to investigate whether ANCA could induce autophagy in the process of NETs formation. Autophagy was detected using live cell imaging, microtubule-associated protein light chain 3B (LC3B) accumulation and Western blotting. The results showed that autophagy vacuolization was detected in neutrophils treated with ANCA-positive IgG by live cell imaging...
September 26, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27670945/regulation-of-the-il-10-driven-macrophage-phenotype-under-incoherent-stimuli
#20
Yishan Chuang, Michelle E Hung, Brianne K Cangelose, Joshua N Leonard
Macrophages are ubiquitous innate immune cells that play a central role in health and disease by adopting distinct phenotypes, which are broadly divided into classical inflammatory responses and alternative responses that promote immune suppression and wound healing. Although macrophages are attractive therapeutic targets, incomplete understanding of this functional choice limits clinical manipulation. While individual stimuli, pathways, and genes involved in macrophage functional responses have been identified, how macrophages evaluate complex in vivo milieus comprising multiple divergent stimuli remains poorly understood...
September 26, 2016: Innate Immunity
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