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Innate Immunity

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https://www.readbyqxmd.com/read/28409545/high-affinity-caspase-4-binding-to-lps-presented-as-high-molecular-mass-aggregates-or-in-outer-membrane-vesicles
#1
Mark A Wacker, Athmane Teghanemt, Jerrold P Weiss, Jason H Barker
Caspases of the non-canonical inflammasome (caspases -4, -5, and -11) directly bind endotoxin (LOS/LPS) and can be activated in the absence of any co-factors. Models of LPS-induced caspase activation have postulated that 1:1 binding of endotoxin monomers to caspase trigger caspase oligomerization and activation, analogous to that established for endotoxin-induced activation of MD-2/TLR4. However, using metabolically radiolabeled LOS and LPS, we now show high affinity and selective binding of caspase-4 to high molecular mass aggregates of purified endotoxin and to endotoxin-rich outer membrane vesicles without formation of 1:1 endotoxin:caspase complexes...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28409544/hypoxia-and-the-hypoxia-regulated-transcription-factor-hif-1%C3%AE-suppress-the-host-defence-of-airway-epithelial-cells
#2
Markus Polke, Frederik Seiler, Philipp M Lepper, Andreas Kamyschnikow, Frank Langer, Dominik Monz, Christian Herr, Robert Bals, Christoph Beisswenger
Chronic diseases of the respiratory tract, such as cystic fibrosis, are associated with mucosal and systemic hypoxia. Innate immune functions of airway epithelial cells are required to prevent and control infections of the lung parenchyma. The transcription factor hypoxia-inducible factor 1α (HIF-1α) regulates cellular adaptation to low oxygen conditions. Here, we show that hypoxia and HIF-1α regulate innate immune mechanisms of cultured human bronchial epithelial cells (HBECs). Exposure of primary HBECs to hypoxia or the prolyl hydroxylase inhibitor dimethyloxaloylglycine (DMOG) resulted in a significantly decreased expression of inflammatory mediators (IL-6, IFN-γ-induced protein 10) in response to ligands for TLRs (flagellin, polyI:C) and Pseudomonas aeruginosa, whereas the expression of inflammatory mediators was not affected by hypoxia or DMOG in the absence of microbial factors...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28409543/ccr-2-neutralization-augments-murine-fresh-bmc-activation-by-staphylococcus-aureus-via-two-distinct-mechanisms-at-the-level-of-ros-production-and-cytokine-response
#3
Ajeya Nandi, Biswadev Bishayi
CCR-2 signaling regulates recruitment of monocytes from the bone marrow into the bloodstream and then to sites of infection. We sought to determine whether CCL-2/CCR-2 signaling is involved in the killing of Staphylococcus aureus by murine bone marrow cells (BMCs). The intermittent link of reactive oxygen species (ROS)-NF-κB/p38-MAPK-mediated CCL-2 production in CCR-2 signaling prompted us to determine whether neutralization of CCR-2 augments the response of murine fresh BMCs (FBMCs) after S. aureus infection...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28409542/inhibitory-receptor-fc%C3%AE-riib-mediates-the-effects-of-igg-on-a-phagosome-acidification-and-a-sequential-dephosphorylation-system-comprising-ships-and-inpp4a
#4
Tomohiro Segawa, Kaoru Hazeki, Kiyomi Nigorikawa, Atsuko Nukuda, Tomoki Tanizawa, Kenshiro Miyamoto, Shin Morioka, Osamu Hazeki
The relative abundance of phosphoinositide (PI) species on the phagosome membrane fluctuates over the course of phagocytosis. PtdIns(3,4,5)P3 and PtdIns(3,4)P2 rapidly increase in the forming of the phagocytic cup, following which they disappear after sealing of the cup. In the present study, we monitored the clearance of these PI species using the enhanced green fluorescent protein-fused pleckstrin homology domain of Akt, a fluorescence probe that binds both PtdIns(3,4,5)P3 and PtdIns(3,4)P2 in Raw 264.7 macrophages...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28409541/a-dual-positive-and-negative-regulation-of-monocyte-activation-by-leukocyte-ig-like-receptor-b4-depends-on-the-position-of-the-tyrosine-residues-in-its-itims
#5
Mijeong Park, Robert W Liu, Hongyan An, Carolyn L Geczy, Paul S Thomas, Nicodemus Tedla
The leukocyte Ig-like receptor B4 (LILRB4) is an inhibitory cell surface receptor, primarily expressed on mono-myeloid cells. It contains 2 C-type Ig-like extracellular domains and a long cytoplasmic domain that contains three intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Data suggest that LILRB4 suppresses Fc receptor-dependent monocyte functions via its ITIMs, but relative contributions of the three ITIMs are not characterised. To address this, tyrosine (Tyr) residues at positions 337, 389 and 419 were single, double or triple mutated to phenylalanine and stably transfected into a human monocytic cell line, THP-1...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28409540/comparison-of-cellular-assays-for-tlr-activation-and-development-of-a-species-specific-reporter-cell-line-for-cattle
#6
Kata Tombácz, Duncan Mwangi, Dirk Werling, Amanda J Gibson
PRRs are sentinels of the innate immune system, with TLRs being the most important. Assays for TLR ligand interactions have been used to gain insights into their function and signaling pathways. As significant differences exist between species with regard to ligand recognition, it is necessary to adapt these tools for TLRs of other species. In the present work, we describe a species-specific cell-based assay adapted for the analysis of single PRRs. Human embryonic kidney 293T cells were stably transfected with the NF-κB-inducible reporter gene secreted embryonic alkaline phosphatase (SEAP) together with bovine TLR2...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28409539/particulate-matter-air-pollution-from-the-city-of-quito-ecuador-activates-inflammatory-signaling-pathways-in%C3%A2-vitro
#7
Victoria M Cevallos, Valeria Díaz, Cherilyn M Sirois
Automobile traffic, industrial processes and natural phenomena cause notable air pollution, including gaseous and particulate contaminants, in urban centers. Exposure to particulate matter (PM) air pollution affects human health, and has been linked to respiratory, cardiovascular and neurological diseases. The mechanisms underlying inflammation in these diverse diseases, and to what extent health effects are different for PM obtained from different sources or locations, are still unclear. This study investigated the in vitro toxicity of ambient course (PM10) and fine (PM2...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28359219/modification-of-sample-processing-for-the-limulus-amebocyte-lysate-assay-enhances-detection-of-inflammogenic-endotoxin-in-intact-bacteria-and-organic-dust
#8
Kimberly A Hoppe Parr, Suzana Hađina, Brita Kilburg-Basnyat, Yifang Wang, Dulce Chavez, Peter S Thorne, Jerrold P Weiss
The pro-inflammatory potency and causal relationship with asthma of inhaled endotoxins have underscored the importance of accurately assessing the endotoxin content of organic dusts. The Limulus amebocyte lysate (LAL) assay has emerged as the preferred assay, but its ability to measure endotoxin in intact bacteria and organic dusts with similar sensitivity as purified endotoxin is unknown. We used metabolically radiolabeled Neisseria meningitidis and both rough and smooth Escherichia coli to compare dose-dependent activation in the LAL with purified endotoxin from these bacteria and shed outer membrane (OM) blebs...
April 2017: Innate Immunity
https://www.readbyqxmd.com/read/28359218/the-critical-role-of-myeloperoxidase-in-streptococcus-pneumoniae-clearance-and-tissue-damage-during-mouse-acute-otitis-media
#9
Yun Xiang, Chunfang Jin, Wei Wang, Zimeng Wang, Yifei Huang, Fangmei Fan, Yurong Ma, Xuemei Zhang, Wenchun Xu, Yibing Yin, Yujuan He
We have recently reported that neutrophils play a pivotal role in innate defense against Streptococcus pneumoniae ( Spn) during mouse acute otitis media (AOM). However, the underlying mechanism remains unclear. By constructing models of pneumococcal AOM in C57BL/6 mice and using a specific inhibitor in vivo, we investigated the role of myeloperoxidase (MPO), one of the most important protein components of neutrophils. Experiment results showed a significant increase in MPO production of the recruited neutrophils in Spn-infected mice...
April 2017: Innate Immunity
https://www.readbyqxmd.com/read/28359217/efferocytosis-induced-prostaglandin-e2-production-impairs-alveolar-macrophage-effector-functions-during-streptococcus-pneumoniae-infection
#10
Ana Cg Salina, Tais P Souza, Carlos H Serezani, Alexandra I Medeiros
Alveolar macrophages (AMs) are multitasking cells that maintain lung homeostasis by clearing apoptotic cells (efferocytosis) and performing antimicrobial effector functions. Different PRRs have been described to be involved in the binding and capture of non-opsonized Streptococcus pneumoniae, such as TLR-2, mannose receptor (MR) and scavenger receptors (SRs). However, the mechanism by which the ingestion of apoptotic cells negatively influences the clearance of non-opsonized S. pneumoniae remains to be determined...
April 2017: Innate Immunity
https://www.readbyqxmd.com/read/28120642/a-novel-mouse-model-of-conditional-irak-m-deficiency-in-myeloid-cells-application-in-lung-pseudomonas-aeruginosa-infection
#11
Di Jiang, Jennifer Matsuda, Reena Berman, Niccolette Schaefer, Connor Stevenson, James Gross, Bicheng Zhang, Amelia Sanchez, Liwu Li, Hong Wei Chu
Myeloid cells such as macrophages are critical to innate defense against infection. IL-1 receptor-associated kinase M (IRAK-M) is a negative regulator of TLR signaling during bacterial infection, but the role of myeloid cell IRAK-M in bacterial infection is unclear. Our goal was to generate a novel conditional knockout mouse model to define the role of myeloid cell IRAK-M during bacterial infection. Myeloid cell-specific IRAK-M knockout mice were generated by crossing IRAK-M floxed mice with LysM-Cre knock-in mice...
February 2017: Innate Immunity
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
#12
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...
February 2017: 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
#13
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...
February 2017: Innate Immunity
https://www.readbyqxmd.com/read/27913792/genetic-engineering-approach-to-develop-next-generation-reagents-for-endotoxin-quantification
#14
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...
February 2017: Innate Immunity
https://www.readbyqxmd.com/read/27884946/analysis-of-the-caenorhabditis-elegans-innate-immune-response-to-coxiella-burnetii
#15
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...
February 2017: Innate Immunity
https://www.readbyqxmd.com/read/28633586/porphyromonas-gingivalis-and-its-lps-differentially-regulate-the-expression-of-peptidyl-arginine-deiminases-in-human-chondrocytes
#16
René Elkaim, Isaac Maximiliano Bugueno-Valdebenito, Nadia Benkirane-Jessel, Henri Tenenbaum
Periodontitis, an inflammatory disease initiated by Gram-negative bacteria such as Porphyromonas gingivalis ( Pg), is considered as a risk factor for rheumatoid arthritis (RA). Our study aimed to determine the effect of Pg and its LPS on the expression of peptidyl arginine deiminase isotypes (PADs) in human primary chondrocytes (HC). HCs were infected with Pg and activated by its LPS (LPS- Pg). The mRNA expression levels of human PADs (1, 2, 3, 4 and 6) and bacterial enzyme (PADPg) were quantified by RT-qPCR...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28606014/tlr2-stimulating-contaminants-in-glycoconjugate-fractions-prepared-from-bacteroides-fragilis
#17
Masahito Hashimoto, Junpei Waki, Haruyuki Nakayama-Imaohji, Mami Ozono, Shuhei Hashiguchi, Tomomi Kuwahara
Bacteroides fragilis is a member of the normal intestinal flora and is involved in host immunostimulation via TLR2. On the bacterial cell surface, glycoconjugates, such as LPS and capsular polysaccharide A (PSA), have been reported to participate in host immunostimulation via TLR2. Previously, we identified a TLR2-stimulating lipoprotein in B. fragilis cells. In this study, we demonstrated that TLR2-stimulating principal molecules in glycoconjugate fractions prepared from B. fragilis are contaminating proteinous molecules, which may also be lipoproteins...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28606013/decrease-of-cd69-levels-on-tcr-v%C3%AE-7-2-cd4-innate-like-lymphocytes-is-associated-with-impaired-cytotoxic-functions-in-chronic-hepatitis-b-virus-infected-patients
#18
Yean K Yong, Hong Y Tan, Alireza Saeidi, Mohamed Rosmawati, Nadia Atiya, Abdul W Ansari, Jayakumar Rajarajeswaran, Jamuna Vadivelu, Vijayakumar Velu, Marie Larsson, Esaki M Shankar
Hepatitis B virus (HBV) infection is a major cause of chronic liver disease that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses represent the key determinants of HBV clearance or persistence. Here, we investigated the role of the early activation marker, CD69 and effector cytokines, granzyme B (GrB) and IFN-γ in the exhaustion of innate-like TCR Vα7.2(+)CD4(+)T cells, in 15 individuals with chronic HBV (CHB) infection where six were HBV DNA(+) and nine were HBV DNA(-)...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28504607/innate-inflammatory-gene-expression-profiling-in-potential-brain-dead-donors-detailed-investigation-of-the-effect-of-common-corticosteroid-therapy
#19
Reza Gholamnezhadjafari, Nader Tajik, Reza Falak, Reza Aflatoonian, Sanaz Dehghan, Abbas Rezaei
Our study aimed to assess the influence of common methylprednisolone therapy on innate inflammatory factors in potential brain-dead organ donors (BDDs). The study groups consisted of 50 potential BDDs who received 15 mg/kg/d methylprednisolone and 25 live organ donors (LDs) as control group. Innate immunity gene expression profiling was performed by RT-PCR array. Soluble serum cytokines and chemokines, complement components, heat shock protein 70 (HSP70) and high mobility group box-1 (HMGB1) were measured by ELISA...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28443393/cd14-gene-silencing-alters-the-microrna-expression-profile-of-raw264-7-cells-stimulated-by-brucella-melitensis-infection
#20
Hui Rong, Hanwei Jiao, Yongchang Hao, Feng Pang, Guohua Li, Dongmei Peng, Yaying Li, Yuanzhi Wang, Hui Zhang, Quanshui Fan, Fengyang Wang, Chuangfu Chen, Li Du
Innate recognition of Brucella spp. is a key step in the activation of inflammation. CD14 binds PAMPs and is involved in LPS-induced pro-inflammatory cytokine release. Previously we showed that knock down of CD14 in RAW264.7 macrophages disrupted Brucella-host interactions. However, its effect on the macrophage microRNA (miRNA) expression profile, especially after stimulation by Brucella infection, is still unclear. To identify miRNAs involved in the macrophage response to Brucella infection, we performed miRNA expression profiling of CD14 knock-down RAW264...
January 1, 2017: Innate Immunity
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