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https://www.readbyqxmd.com/read/28931237/histone-methyltransferase-set8-epigenetically-reprograms-host-immune-responses-to-assist-mycobacterial-survival
#1
Vikas Singh, Praveen Prakhar, R S Rajmani, Kasturi Mahadik, Salik Miskat Borbora, Kithiganahalli Narayanaswamy Balaji
NQO1 and TRXR1 are important host reductases implicated in the regulation of inflammation and apoptosis. Although the transcriptional machinery governing these processes have been extensively investigated, the associated epigenetic regulatory events remain unclear. Here, we report that SET8, a histone H4 lysine 20 monomethylase (H4K20me1), is highly induced during Mycobacterium tuberculosis infection that orchestrates immune evasion strategies through the induction of NQO1 and TRXR1 in vivo. SET8, along with FoxO3a, mediates an active NQO1-PGC1-α complex, which promotes the anti-inflammatory M2 macrophage phenotype, and assists TRXR1-regulated arrest of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28931235/monoclonal-antibody-protects-against-acinetobacter-baumannii-infection-by-enhancing-bacterial-clearance-and-evading-sepsis
#2
Travis B Nielsen, Paul Pantapalangkoor, Brian M Luna, Kevin W Bruhn, Jun Yan, Ken Dekitani, Sarah Hsieh, Brandon Yeshoua, Bryan Pascual, Evgeny Vinogradov, Kristine M Hujer, T Nicholas Domitrovic, Robert A Bonomo, Thomas A Russo, Magda Lesczcyniecka, Thomas Schneider, Brad Spellberg
Background: Extremely drug-resistant (XDR) Acinetobacter baumannii is one of the most commonly encountered, highly resistant pathogens requiring novel therapeutic interventions. Methods: We developed C8, a monoclonal antibody (mAb), by immunizing mice with sublethal inocula of a hypervirulent XDR clinical isolate. Results: C8 targets capsular carbohydrate on the bacterial surface, enhancing opsonophagocytosis. Treating with a single dose of C8 as low as 0...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28930915/microvesicle-subsets-in-sepsis-due-to-community-acquired-pneumonia-compared-to-faecal-peritonitis
#3
Hazem M S Lashin, Suchita Nadkarni, Silvia Oggero, Hefin R Jones, Julian C Knight, Charles J Hinds, Mauro Perretti
RATIONALE: Microvesicles (MV) act as a non-soluble means of inter-cellular communication, with effector roles in disease pathogenesis and potentially as biomarkers. Previously, we reported that neutrophil MV expressing alpha-2-macroglobulin (A2MG) are protective in experimental sepsis and associate with survival in a small cohort of patients with sepsis due to community acquired pneumonia (CAP). OBJECTIVES: To characterise MV profiles in sepsis due to CAP or faecal peritonitis (FP) and determine their relation to outcome...
September 19, 2017: Shock
https://www.readbyqxmd.com/read/28930653/fishing-for-answers-in-human-mycobacterial-infections
#4
Miriam Bolz, Joel D Ernst
Two recent studies (Cambier et al., 2017; Madigan et al., 2017) reveal in vivo functions for specific phenolic glycolipids (PGLs) in the mycobacteria that cause tuberculosis or leprosy. M. tuberculosis (and M. marinum) PGL promotes bacterial spread to growth-permissive macrophages, while M. leprae PGL-1 induces macrophages to cause nerve demyelination characteristic of human leprosy.
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930616/development-of-a-semi-automated-image-based-high-throughput-drug-screening-system
#5
Remzi Onur Eren, Dmitry Kopelyanskiy, Dimitri Moreau, Julien Bortoli Chapalay, Marc Chambon, Gerardo Turcatti, Lon-Fye Lye, Stephen M Beverley, Nicolas Fasel
We previously reported that the innate sensing of the endosymbiont Leishmania RNA virus 1 (LRV1) within Leishmania (Viannia) guyanensis through Toll-like receptor 3, worsens the pathogenesis of parasite infection in mice. The presence of LRV1 has been associated with the failure of first-line treatment in patients infected with LRV1 containing -L. guyanensis and -L. braziliensis parasites. Here, we established a semi-automated image-based high-throughput drug screening (HTDS) protocol to measure parasiticidal activity of the Prestwick chemical library in primary murine macrophages infected with LRV1-containing L...
January 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/28930253/in-vitro-and-in-vivo-evaluation-of-essential-oil-from-artemisia-absinthium-l-formulated-in-nanocochleates-against-cutaneous-leishmaniasis
#6
Beatriz Tamargo, Lianet Monzote, Abel Piñón, Laura Machín, Marley García, Ramón Scull, William N Setzer
Background: Leishmaniasis is a zoonotic disease caused by protozoan parasites from Leishmania genus. Currently, there are no effective vaccines available and the available therapies are far from ideal. In particular, the development of new therapeutic strategies to reduce the infection caused by Leishmania amazonensis could be considered desirable. Different plant-derived products have demonstrated antileishmanial activity, including the essential oil (EO) from Artemisia absinthium L. (EO-Aa), Asteraceae. Methods: In the present study, the EO-Aa formulated in nanocochleates (EO-Aa-NC) was investigated in vitro against intracellular amastigotes of L...
June 9, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28929503/induction-of-heme-oxygenase-1-increases-infection-of-dog-macrophages-by-l-infantum
#7
Breno Fernando Martins de Almeida, Kathlenn Liezbeth Oliveira Silva, Gabriela Lovizutto Venturin, Vanessa Marim Chiku, Aline Aparecida Correa Leal, Anelise Maria Bosco, Paulo Cesar Ciarlini, Valéria Marçal Felix de Lima
AIMS: We aimed to induce and inhibit HO-1, ascertaining its effect on infection rate, parasite load and the levels of superoxide, reactive oxygen species (ROS), nitric oxide (NO), TNF-alpha and IL-10 in cultured macrophages from healthy dogs infected by Leishmania infantum. METHODS AND RESULTS: Macrophages obtained from 15 healthy dogs were cultured alone or infected with L. infantum, with or without association of HO-1 inducer and inhibitor. The infection rate and the parasite load were determined by the number of infected macrophages and number of promastigotes per macrophage, respectively...
September 20, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28929313/an-anti-propionibacterium-acnes-antibody-shows-heterologous-resistance-to-an-actinobacillus-pleuropneumoniae-infection-independent-of-neutrophils-in-mice
#8
Jian-Fang Liu, Qiu-Yue Ma, Ri-Ning Zhu, Meng-Jun Cheng, Chun-Tong Bao, Jing-Min Gu, Chang-Jiang Sun, Paul Richard Langford, Wen-Yu Han, Lian-Cheng Lei
Porcine contagious pleuropneumonia is a highly fatal respiratory disease that is caused by Actinobacillus pleuropneumoniae (APP) and results in tremendous economic losses for the pig breeding industry worldwide. Previous studies have demonstrated that Propionibacterium acnes (PA) could effectively prevent APP infection in mice and pigs. The humoral immune response played a primary role during this process and anti-PA antibody could mediate macrophages to kill the bacteria. However, the role of neutrophils in this process is currently unknown...
September 20, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28928941/computational-design-of-molecular-motors-as-nanocircuits-in-leishmaniasis
#9
Dipali Kosey, Shailza Singh
Cutaneous leishmaniasis is the most common form of lesihmaniasis, caused by Leishmania major and is spread by the bite of a sandfly .This species infects the macrophages and dendritic cells Due to multi-drug resistance, there is a need for a new therapeutic technique. Recently, a novel molecular motor of Leishmania, Myosin XXI, was classified and characterized. In addition, the drug resistance in this organism has been linked with the overexpression of ABC transporters. Systems biology aims to study the simulation and modeling of natural biological systems whereas synthetic biology deals with building novel and artificial biological parts and devices  Together they have contributed enormously to drug discovery, vaccine design and development, infectious disease detection and diagnostics...
2017: F1000Research
https://www.readbyqxmd.com/read/28927902/characterisation-of-a-novel-coumarin-based-fluorescent-probe-for-monitoring-nitric-oxide-production-in-macrophages
#10
Maiada M Sadek, Mina Barzegar Amiri Olia, Cameron J Nowell, Νicholas Barlow, Carl H Schiesser, Sandra E Nicholson, Raymond S Norton
Nitric oxide (NO) is an important effector molecule in host defence against bacterial pathogens. The development of fluorescence imaging to monitor NO production in vitro and in vivo will increase our understanding of its biological role. Recently, a novel 'trappable' fluorescent blue 'turn-on' Cu(II)-complexed coumarin-based probe (CB) has been developed to detect NO. In this study, CB was investigated to evaluate its ability to detect NO in macrophages. Using confocal microscopy, NO was successfully detected in macrophages in the presence of stimuli that induce nitric oxide synthase (iNOS), the enzyme responsible for production of NO...
September 5, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28927767/gem-dithioacetylated-indole-derivatives-as-novel-antileishmanial-agents
#11
Sharad Porwal, Suman Gupta, Prem M S Chauhan
In this communication we report a serendipitously discovered hybrid molecule 1, combining fragment of 3 (an in vivo active antileishmanial molecule) with H2S donor moiety (known for bimodal behavior of cytoprotection and apoptosis), as antileishmanial agent. Compound 1 suppresses 99.82% parasitemia of L. donovani infected macrophages at 12.5μg/ml without even deforming them (CC50>100μg/ml). This compound appears cytotoxic for intracellular amastigotes while cytoprotective to host macrophages. The concept can be utilized to develop high therapeutic index NCE (New Chemical Entities) for other macrophage mediated diseases like tuberculosis and cancer...
September 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28926773/dectin-1-is-essential-for-il-1%C3%AE-production-through-jnk-activation-and-apoptosis-in-aspergillus-fumigatus-keratitis
#12
Kelan Yuan, Guiqiu Zhao, Chengye Che, Cui Li, Jing Lin, Guoqiang Zhu, Kun He
PURPOSE: To investigate the role of phosphorylated JNK in Dectin-1-induced IL-1β production and the role of Dectin-1 in apoptosis in mouse Aspergillus fumigatus (A. fumigatus) keratitis. METHODS: Mice corneas were pretreated with Dectin-1 siRNA or SP600125 (the inhibitor of JNK) before A. fumigatus infection. THP-1 macrophages were preincubated with SP600125 before the stimulation of A. fumigatus conidia. Dectin-1, IL-1β, JNK, Bax, Bcl-2, cytochrome-c (cyt-c), caspase-9, caspase-8 and caspase-3 expressions were tested by PCR, Western blot, or Immunofluorescence staining...
September 16, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28924204/cyclipostins-and-cyclophostin-analogs-as-promising-compounds-in-the-fight-against-tuberculosis
#13
Phuong Chi Nguyen, Vincent Delorme, Anaïs Bénarouche, Benjamin P Martin, Rishi Paudel, Giri R Gnawali, Abdeldjalil Madani, Rémy Puppo, Valérie Landry, Laurent Kremer, Priscille Brodin, Christopher D Spilling, Jean-François Cavalier, Stéphane Canaan
A new class of Cyclophostin and Cyclipostins (CyC) analogs have been investigated against Mycobacterium tuberculosis H37Rv (M. tb) grown either in broth medium or inside macrophages. Our compounds displayed a diversity of action by acting either on extracellular M. tb bacterial growth only, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth with very low toxicity towards host macrophages. Among the eight potential CyCs identified, CyC 17 exhibited the best extracellular antitubercular activity (MIC50 = 500 nM)...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924090/porcine-alveolar-macrophage-polarization-is-involved-in-inhibition-of-porcine-reproductive-and-respiratory-syndrome-virus-prrsv-replication
#14
Longtao Wang, Shouping Hu, Qiang Liu, Yiru Li, Lu Xu, Zhuo Zhang, Xuehui Cai, Xijun He
Macrophage polarization is a process by which macrophages acquire a distinct phenotypic and functional profile in response to microenvironmental signals. The classically and alternatively activated (M1 and M2, respectively) macrophage phenotypes are defined by the specific molecular characteristics induced in response to prototypic pro- and anti-inflammatory cues. In this study, we used LPS/IFN-γ and IL-4 to stimulate porcine alveolar macrophages (PAMs) in vitro and investigated the expression changes of several novel markers during macrophage polarization...
September 17, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28923131/innate-and-adaptive-immune-response-to-chronic-pulmonary-infection-of-hyphae-of-aspergillus-fumigatus-in-a-new-murine-model
#15
Fengyuan Wang, Caiyun Zhang, Yuan Jiang, Caixia Kou, Qingtao Kong, Nanbiao Long, Ling Lu, Hong Sang
PURPOSE: The pathogenesis of chronic pulmonary aspergillosis (CPA) has seldom been studied due partly to a lack of animal models. Since hypha is the main morphology colonizing the airway in CPA, it's critical to study the immune reaction to chronic pulmonary infection of hyphae of Aspergillus fumigatus, which also has seldom been studied in vivo before. METHODOLOGY: We established a novel murine model of chronic pulmonary infection of hyphae by challenging immunocompetent mice with tightly-structured hyphae balls intratracheally, and described the ensuing immunoreaction to hyphae and conidia, and the pathogenesis of CPA...
September 19, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28922809/a-novel-ceftazidime-avibactam-rifabutin-tedizolid-and-moxifloxacin-cartm-regimen-for-pulmonary-mycobacterium-avium-disease
#16
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Pooi S Lee, Tawanda Gumbo
Objectives: To compare the efficacy of ceftazidime/avibactam plus tedizolid-based combination regimens with the standard therapy of azithromycin, ethambutol and rifabutin for the treatment of pulmonary Mycobacterium avium complex (MAC) disease. Methods: We mimicked the human pulmonary concentration-time profiles of ceftazidime/avibactam and tedizolid in combination, ceftazidime/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM), and the standard regimen and examined microbial kill in triplicate hollow-fibre system model of intracellular pulmonary MAC (HFS-MAC) units...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922635/fucoidan-coated-ciprofloxacin-loaded-chitosan-nanoparticles-for-the-treatment-of-intracellular-and-biofilm-infections-of-salmonella
#17
Elbi S, Nimal T R, Rajan V K, Gaurav Baranwal, Raja Biswas, Jayakumar R, Sathianarayanan S
Salmonella infections and their gallstone associated biofilm infections are difficult to treat due to poor penetration of antibiotics into the intracellular compartments of macrophages and within biofilms. Here we developed ciprofloxacin loaded chitosan nanoparticles (cCNPs) and fucoidan (Fu) coated cCNPs (Fu-cCNPs). Characterizations of these nanoparticles were carried out using Dynamic Light Scattering‎, Transmission electron microscopy and Fourier transform infrared spectroscopy. The prepared cCNPs and Fu-cCNPs have the size range of 124±7nm and 320±18nm, respectively...
September 5, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28922390/identifying-novel-transcription-factors-involved-in-the-inflammatory-response-by-using-binding-site-motif-scanning-in-genomic-regions-defined-by-histone-acetylation
#18
Peter S Askovich, Stephen A Ramsey, Alan H Diercks, Kathleen A Kennedy, Theo A Knijnenburg, Alan Aderem
The innate immune response to pathogenic challenge is a complex, multi-staged process involving thousands of genes. While numerous transcription factors that act as master regulators of this response have been identified, the temporal complexity of gene expression changes in response to pathogen-associated molecular pattern receptor stimulation strongly suggest that additional layers of regulation remain to be uncovered. The evolved pathogen response program in mammalian innate immune cells is understood to reflect a compromise between the probability of clearing the infection and the extent of tissue damage and inflammatory sequelae it causes...
2017: PloS One
https://www.readbyqxmd.com/read/28921465/emerging-roles-for-epigenetic-programming-in-the-control-of-inflammatory-signaling-integration-in-heath-and-disease
#19
Yiqun Hu, Feng Yan, Le Ying, Dakang Xu
Macrophages and dendritic cells initiate the innate immune response to infection and injury and contribute to inflammatory signaling to maintain the homeostasis of various tissues, which includes resident macrophages for the elimination of invading microorganisms and tissue damage. Inappropriate inflammatory signaling can lead to persistent inflammation and further develop into autoimmune and inflammation-associated diseases. Inflammatory signaling pathways have been well characterized, but how these signaling pathways are converted into sustained and diverse patterns of expression of cytokines, chemokines, and other genes in response to environmental challenges is unclear...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28921048/antibacterial-and-antitumor-activity-of-bogorol-b-jx-isolated-from-brevibacillus-laterosporus-jx-5
#20
Hongxia Jiang, Chao Ji, Junkang Sui, Rongbo Sa, Xiaohui Wang, Xunli Liu, Tai L Guo
Antimicrobial peptides are promising anti-infective agent candidates because they have a broad antimicrobial spectrum and bioactivity and are unlikely to elicit antibiotic resistance. The bogorols represent a new cationic antibiotic peptide and possess great therapeutic potential because of their bioactivity and precise mode of action. Here, we report that Bogorol B-JX (BBJX), a peptide previously isolated from Brevibacillus laterosporus JX-5 by us, has significant antibacterial and antitumor activities in vitro...
September 18, 2017: World Journal of Microbiology & Biotechnology
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