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macrophage tuberculosis

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https://www.readbyqxmd.com/read/28318770/expression-of-cathepsin-s-in-bcg-converts-it-into-a-pro-apoptotic-and-highly-immunogenic-strain
#1
Alice Lau, Vijender Singh, Hafid Soualhine, Zakaria Hmama
BACKGROUND: BCG vaccine, introduced almost 100years ago, is the only option to prevent TB disease. It effectively protects newborns from meningeal TB but fails to prevent adult pulmonary TB. TB kills 1.3million people annually in areas where BCG vaccination is widely practiced. Thus, more effective TB vaccines are urgently needed. Others and we have shown that BCG mimics features of virulent M. tuberculosis, in particular attenuation of essential macrophage functions such as phagosome maturation and antigen presentation...
March 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28317816/hemophagocytic-syndrome-secondary-to-tuberculosis-at-24-week-gestation
#2
Alexandra Arteaga Fernández, David Fernández de Velasco Pérez, M C Jiménez Fournier, J C Moreno Del Prado, B Paraíso Torras, M L Cañete Palomo
Hemophagocytic syndrome is a life-threatening disease characterized by the uncontrolled activation of macrophages, resulting in hemophagocytosis of blood cells in the bone marrow. A 20-year-old gravida at 23-week and 5-day gestation was admitted to hospital to evaluate fever up to 104°F of unknown origin, moderate cytopenia, and elevated levels of liver enzymes. Bone marrow biopsy confirmed hemophagocytic syndrome, and polymerase chain reaction came back positive for Mycobacterium tuberculosis. Supportive care and tuberculosis treatment resulted in clinical improvement...
January 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28306733/hypervirulent-mycobacterium-tuberculosis-strain-triggers-necrotic-lung-pathology-associated-with-enhanced-recruitment-of-neutrophils-in-resistant-c57bl-6-mice
#3
Fabrício M Almeida, Thatiana L B Ventura, Eduardo P Amaral, Simone C M Ribeiro, Sanderson D Calixto, Marcelle R Manhães, Andreza L Rezende, Giliane S Souzal, Igor S de Carvalho, Elisangela C Silva, Juliana Azevedo da Silva, Eulógio C Q Carvalho, Afranio L Kritski, Elena B Lasunskaia
Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) that in most cases induces irreversible necrosis of lung tissue as a result of excessive inflammatory reactions. The murine model of TB in resistant C57BL/6 mice infected with reference Mtb strains is widely used in TB studies; however, these mice do not show a necrotic pathology, which restricts their use in studies of irreversible tissue damage. Recently, we demonstrated that necrotic lung lesions could be induced in the C57BL/6 mice by highly virulent Mtb strains belonging to the modern Beijing sublineage...
2017: PloS One
https://www.readbyqxmd.com/read/28306498/elevation-of-fumarate-levels-compromise-redox-control-and-viability-in-mycobacterium-tuberculosis
#4
Yong-Mo Ahn, Helena I Boshoff
In this issue of Cell Chemical Biology, Ruecker et al. (2017) show that fumarase depletion in Mycobacterium tuberculosis leads to fumarate, a TCA cycle intermediate, accumulation, causing succination of a range of thiol-containing metabolites and proteins. Fumarate is bactericidal to the pathogen, and its accumulation may enhance the bactericidal effector mechanisms of other TCA cycle intermediates that accumulate due to activation of infected macrophages.
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28293236/interferon-lambda-modulating-immunity-in-infectious-diseases
#5
REVIEW
Mohammedyaseen Syedbasha, Adrian Egli
Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28288970/mycobacterium-tuberculosis-cpn60-2-groel2-blocks-macrophage-apoptosis-via-interaction-with-mitochondrial-mortalin
#6
Sunil Joseph, Alex Yuen, Vijender Singh, Zakaria Hmama
Earlier studies suggested that Mycobacterium tuberculosis (Mtb) proteins exported within the host macrophage play an essential role in tuberculosis pathogenesis. In fact, Mtb proteins interact with and deactivate key regulators of many macrophage functions such as phago-lysosome fusion and antigen presentation, resulting in the intracellular persistence of pathogenic mycobacteria. Cpn60.2 is an abundant Mtb chaperone protein, restricted to cell cytoplasm and surface, that was reported to be essential for bacterial growth...
March 13, 2017: Biology Open
https://www.readbyqxmd.com/read/28281912/naphthofuroquinone-derivatives-show-strong-antimycobacterial-activities-against-drug-resistant-mycobacteria
#7
Woong Sik Jang, Young-Sang Choi, Sukyung Kim, Md Anirban Jyoti, Hoonhee Seo, Juhye Han, Yong-Sik Kim, Jiwon Lyu, Kung-Woo Nam, Byung-Eui Lee, Kee-In Lee, Ho-Yeon Song
Tuberculosis, one of the world's major health problems, has become more serious due to the emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (MTB). In this study, we performed three anti-MTB assays to evaluate the anti-mycobacterial activity of naphthofuroquinone derivatives against drug-resistant MTB. Among them, methyl 5-[2-(dimethylamino)ethoxy]-7,12-dioxo-7,12-dihydrodinaphtho[1,2-b:2',3'-d]furan-6-carboxylate (DFC2) exhibited strong anti-mycobacterial activity against MTB H37Ra, H37Rv and four drug-resistant MTB strains...
March 10, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/28276697/the-crosstalk-between-sphingomyelinases-and-reactive-oxygen-species-in-mycobacterial-infection
#8
Yuqing Wu, Erich Gulbins, Heike Grassme
SIGNIFICANCE: Tuberculosis (TB), which is caused by Mycobacterium tuberculosis, is one of the most important infections worldwide. The sphingomyelinase/ceramide system, which has been shown to be a crucial factor in internalizing and killing various pathogens, modulates both the pro-inflammatory response and the state of mycobacteria in macrophages. However, studies about the role of sphingomyelinases in TB are still at an early stage. Recent Advances: Recent studies elucidated several roles of sphingomyelinases in manipulating mycobacterial infections...
March 9, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28275133/ppar-%C3%AE-activation-mediates-innate-host-defense-through-induction-of-tfeb-and-lipid-catabolism
#9
Yi Sak Kim, Hye-Mi Lee, Jin Kyung Kim, Chul-Su Yang, Tae Sung Kim, Mingyu Jung, Hyo Sun Jin, Sup Kim, Jichan Jang, Goo Taeg Oh, Jin-Man Kim, Eun-Kyeong Jo
The role of peroxisome proliferator-activated receptor α (PPAR-α) in innate host defense is largely unknown. In this study, we show that PPAR-α is essential for antimycobacterial responses via activation of transcription factor EB (TFEB) transcription and inhibition of lipid body formation. PPAR-α deficiency resulted in an increased bacterial load and exaggerated inflammatory responses during mycobacterial infection. PPAR-α agonists promoted autophagy, lysosomal biogenesis, phagosomal maturation, and antimicrobial defense against Mycobacterium tuberculosis or M...
March 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28272457/novel-vaccine-potential-of-rv3131-a-dosr-regulon-encoded-putative-nitroreductase-against-hyper-virulent-mycobacterium-tuberculosis-strain-k
#10
Kee Woong Kwon, Woo Sik Kim, Hongmin Kim, Seung Jung Han, Mi-Young Hahn, Jong Seok Lee, Ki Taek Nam, Sang-Nae Cho, Sung Jae Shin
Accumulating evidence indicates that latency-associated Mycobacterium tuberculosis (Mtb)-specific antigens from the dormancy survival regulator regulon (DosR) may be promising novel vaccine target antigens for the development of an improved tuberculosis vaccine. After transcriptional profiling of DosR-related genes in the hyper-virulent Beijing Mtb strain K and the reference Mtb strain H37Rv, we selected Rv3131, a hypothetical nitroreductase, as a vaccine antigen and evaluated its vaccine efficacy against Mtb K...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28268597/an-in-silico-model-of-the-effects-of-vitamin-d3-on-mycobacterium-infected-macrophage
#11
Maya Gough, Elebeoba May
Mycobacterium tuberculosis is a global health concern, causing over one million deaths a year. Alveolar macrophages, as the primary host cell of this intracellular bacterium, play an important role in the course of disease. Vitamin D3 is known to have a potent effect on macrophage behavior during infection, modulating the production of pro- and anti-inflammatory cytokines and immune effector molecules. In a vitamin D3 deficient host, the immune systems response to infection is greatly impaired. We used a quantitative systems biology approach to model the intracellular effects of vitamin D3 and compared our simulation output to our in vitro model of mycobacterium infection of macrophages in the presence and absence of Vitamin D3...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28262829/exosomes-function-in-antigen-presentation-during-an-in-vivo-mycobacterium-tuberculosis-infection
#12
Victoria L Smith, Yong Cheng, Barry R Bryant, Jeffrey S Schorey
Mycobacterium tuberculosis-infected macrophages and dendritic cells are limited in their ability to present antigen to CD4+ T cells suggesting that other mechanism of antigen presentation are driving the robust T cell response observed during an M. tuberculosis infection. These mechanisms could include antigens present in apoptotic bodies, necrotic debris, exosomes or even release of non-vesicular antigen from infected cells. However, there is limited data to support any of these mechanisms as important in driving T cell activation in vivo...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28262681/regulation-of-phagocyte-triglyceride-by-a-stat-atg2-pathway-controls-mycobacterial-infection
#13
Claire B Péan, Mark Schiebler, Sharon W S Tan, Jessica A Sharrock, Katrin Kierdorf, Karen P Brown, M Charlotte Maserumule, Shinelle Menezes, Martina Pilátová, Kévin Bronda, Pierre Guermonprez, Brian M Stramer, R Andres Floto, Marc S Dionne
Mycobacterium tuberculosis remains a global threat to human health, yet the molecular mechanisms regulating immunity remain poorly understood. Cytokines can promote or inhibit mycobacterial survival inside macrophages and the underlying mechanisms represent potential targets for host-directed therapies. Here we show that cytokine-STAT signalling promotes mycobacterial survival within macrophages by deregulating lipid droplets via ATG2 repression. In Drosophila infected with Mycobacterium marinum, mycobacterium-induced STAT activity triggered by unpaired-family cytokines reduces Atg2 expression, permitting deregulation of lipid droplets...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28257432/alternate-splicing-of-transcripts-shape-macrophage-response-to-mycobacterium-tuberculosis-infection
#14
Haroon Kalam, Mary F Fontana, Dhiraj Kumar
Transcriptional reprogramming of macrophages upon Mycobacterium tuberculosis (Mtb) infection is widely studied; however, the significance of alternate splicing (AS) in shaping cellular responses to mycobacterial infections is not yet appreciated. Alternate splicing can influence transcript stability or structure, function and localization of corresponding proteins thereby altering protein stoichiometry and physiological consequences. Using comprehensive analysis of a time-series RNA-seq data obtained from human macrophages infected with virulent or avirulent strains of Mtb, we show extensive remodeling of alternate splicing in macrophage transcriptome...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28249101/azido-pentoses-a-new-tool-to-efficiently-label-mycobacterium-tuberculosis-clinical-isolates
#15
Katharina Kolbe, Leonhard Möckl, Victoria Sohst, Julius Brandenburg, Regina Engel, Sven Malm, Christoph Bräuchle, Otto Holst, Thisbe K Lindhorst, Norbert Reiling
Mycobacterium tuberculosis (Mtb), the main causative agent of tuberculosis (Tb), has a complex cell envelope which forms an efficient barrier to antibiotic stress, contributing to the obstacles of anti-tuberculosis therapy. However, the uniqueness of the Mtb cell wall can be considered an advantage and be utilized to selectively label Mtb bacteria. Here we introduce three azido pentoses, 3 azido arabinose (3AraAz), 3-azido ribose (3RiboAz) and 5-azido arabinofuranose (5AraAz), as new compounds for metabolic labeling of Mtb...
March 1, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28247861/novel-role-for-il-22-in-protection-during-chronic-mycobacterium-tuberculosis-hn878-infection
#16
P Treerat, O Prince, A Cruz-Lagunas, M Muñoz-Torrico, M A Salazar-Lezama, M Selman, B Fallert-Junecko, T A Reinhardt, J F Alcorn, D Kaushal, J Zuñiga, J Rangel-Moreno, J K Kolls, S A Khader
Approximately 2 billion people are infected with Mycobacterium tuberculosis (Mtb), resulting in 1.4 million deaths every year. Among Mtb-infected individuals, clinical isolates belonging to the W-Beijing lineage are increasingly prevalent, associated with drug resistance, and cause severe disease immunopathology in animal models. Therefore, it is exceedingly important to identify the immune mechanisms that mediate protection against rapidly emerging Mtb strains, such as W-Beijing lineage. IL-22 is a member of the IL-10 family of cytokines with both protective and pathological functions at mucosal surfaces...
March 1, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28242744/mycobacterium-tuberculosis-replicates-within-necrotic-human-macrophages
#17
Thomas R Lerner, Sophie Borel, Daniel J Greenwood, Urska Repnik, Matthew R G Russell, Susanne Herbst, Martin L Jones, Lucy M Collinson, Gareth Griffiths, Maximiliano G Gutierrez
Mycobacterium tuberculosis modulation of macrophage cell death is a well-documented phenomenon, but its role during bacterial replication is less characterized. In this study, we investigate the impact of plasma membrane (PM) integrity on bacterial replication in different functional populations of human primary macrophages. We discovered that IFN-γ enhanced bacterial replication in macrophage colony-stimulating factor-differentiated macrophages more than in granulocyte-macrophage colony-stimulating factor-differentiated macrophages...
March 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28240248/essentiality-of-mmpl3-and-impact-of-its-silencing-on-mycobacterium-tuberculosis-gene-expression
#18
Giulia Degiacomi, Andrej Benjak, Jan Madacki, Francesca Boldrin, Roberta Provvedi, Giorgio Palù, Jana Kordulakova, Stewart T Cole, Riccardo Manganelli
MmpL3 is an inner membrane transporter of Mycobacterium tuberculosis responsible for the export of trehalose momomycolate, a precursor of the mycobacterial outer membrane component trehalose dimycolate (TDM), as well as mycolic acids bound to arabinogalactan. MmpL3 represents an emerging target for tuberculosis therapy. In this paper, we describe the construction and characterization of an mmpL3 knockdown strain of M. tuberculosis. Downregulation of mmpL3 led to a stop in bacterial division and rapid cell death, preceded by the accumulation of TDM precursors...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28237876/passive-transfer-of-interferon-%C3%AE-over-expressing-macrophages-enhances-resistance-of-scid-mice-to-mycobacterium-tuberculosis-infection
#19
Rajamouli Pasula, William J Martin, Banu Rekha Kesavalu, Maher Y Abdalla, Bradley E Britigan
Infection with Mycobacterium tuberculosis (M.tb) is associated with increased deaths worldwide. Alveolar macrophages (AMs) play a critical role in host defense against infection with this pathogen. In this work we tested the hypothesis that passive transfer of normal AMs, IFN-γ activated AMs, or macrophages transduced to over-express IFN-γ into the lungs of immunosuppressed SCID mice, where resident macrophages are present but not functional, would enhance alveolar immunity and increase clearance of pulmonary M...
February 23, 2017: Cytokine
https://www.readbyqxmd.com/read/28237032/sclerotiorin-inhibits-protein-kinase-g-from-mycobacterium-tuberculosis-and-impairs-mycobacterial-growth-in-macrophages
#20
Dongni Chen, Shuangshuang Ma, Lei He, Peibo Yuan, Zhigang She, Yongjun Lu
As a eukaryotic-like Ser/Thr protein kinase, Mycobacterium tuberculosis virulent effector protein kinase G (PknG) mediates mycobacterial survival by regulating bacterial cell metabolic processes and preventing phagosome-lysosome fusion in host macrophages. Targeting PknG is an effective strategy for development of anti-tuberculosis (TB) drugs. In the study, we found that sclerotiorin, derived from marine fungi from the South China Sea, exhibited moderately strong inhibitory effects on recombinant PknG, with an IC50 value of 76...
March 2017: Tuberculosis
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