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macrophage tuberculosis

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https://www.readbyqxmd.com/read/28816372/in-vitro-antitubercular-activity-of-3-deoxysappanchalcone-isolated-from-the-heartwood-of-caesalpinia-sappan-linn
#1
Hoonhee Seo, Sukyung Kim, Hafij Al Mahmud, Md Imtiazul Islam, Kung-Woo Nam, Byung-Eui Lee, Hanna Lee, Myoung-Lae Cho, Heung-Mook Shin, Ho-Yeon Song
Responsible for nearly 1.5 million deaths every year, the infectious disease tuberculosis remains one of the most serious challenges to global health. The emergence of multidrug-resistant tuberculosis and, more recently, extensively drug-resistant tuberculosis poses a significant threat in our effort to control this epidemic. New drugs are urgently needed to combat the growing threat of antimicrobial resistance. To achieve this goal, we screened approximately 500 species of medicinal plant methanol extracts and their solvent partitioned fractions for potential inhibitors of Mycobacterium tuberculosis growth...
August 17, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28808382/allium-sativum-constituents-exhibit-anti-tubercular-activity-in-vitro-and-in-raw-264-7-mouse-macrophage-cells-infected-with-mycobacterium-tuberculosis-h37rv
#2
Swapna S Nair, Sujay S Gaikwad, Savita P Kulkarni, Alka Pravin Mukne
BACKGROUND: Long duration of treatment, side-effects of currently used anti-tubercular drugs and emergence of drug-resistant forms of Mycobacterium tuberculosis (MTB) warrants the need to develop new drugs to tackle the scourge of tuberculosis (TB). Garlic is an edible plant reported to have anti-tubercular activity. However, previous researches on anti-tubercular effect of garlic were focused mostly on preliminary in vitro screening. OBJECTIVE: To identify constituents responsible for anti-tubercular activity of thiosulfinate-derivative rich extract of garlic (GE) and to evaluate activity of the most active constituent in RAW 264...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28802408/down-regulation-of-malate-synthase-in-mycobacterium-tuberculosis-h37ra-leads-to-reduced-stress-tolerance-persistence-and-survival-in-macrophages
#3
Kumar Sachin Singh, Rishabh Sharma, Deepa Keshari, Nirbhay Singh, Sudheer Kumar Singh
Malate synthase is a condensing enzyme responsible for conversion of glyoxylate to malate in the presence of acetyl-CoA. This reaction helps in bypassing the TCA cycle reactions involving carbon loss and leads to diverting some of the carbon skeletons to gluconeogenic events while rest can continue to provide TCA cycle intermediates. Malate synthase (GlcB) is encoded by MRA_1848 of Mycobacterium tuberculosis H37Ra (Mtb-Ra). We developed a knockdown (KD) Mtb-Ra strain by down-regulating GlcB. The survival studies suggested increased susceptibility to oxidative and nitrosative stress as well as to rifampicin...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28802400/mycobacterium-tuberculosis-myma-is-a-tlr2-agonist-that-activate-macrophages-and-a-th1-response
#4
Iti Saraav, Swati Singh, Kirti Pandey, Monika Sharma, Sadhna Sharma
Cell wall of Mycobacterium tuberculosis (M.tb) is a major source of immunogenic proteins that can be tested as vaccine candidates. MymA (Rv3083), a 55 kDa M.tb flavin containing monooxygenase, is involved in modification of mycolic acids during acidic shock following M.tb internalization in macrophage. In this study, we have investigated the role of this cell wall associated protein in activation of macrophages by toll like receptor (TLRs) engagement and subsequent signaling. Our results showed that MymA stimulation of THP1 cells and human monocyte derived macrophages (MDM) lead to upregulation of TLR2 and co-stimulatory molecules CD40, CD80, CD86 and HLA-DR...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28802397/lysx-gene-is-differentially-expressed-among-mycobacterium-tuberculosis-strains-with-different-levels-of-virulence
#5
Alejandra Montoya-Rosales, Roberta Provvedi, Flor Torres-Juarez, Jose A Enciso-Moreno, Rogelio Hernandez-Pando, Riccardo Manganelli, Bruno Rivas-Santiago
Antimicrobial peptides (AMPs) are mainly produced by epithelial cells and macrophages to eliminate infecting mycobacteria through direct antimicrobial activity and immunomodulation. Indeed, it has been described that this line of defense is essential to control infection. However, Mycobacterium tuberculosis (Mtb) has developed mechanisms to avoid AMPs activity, for instance lysX adds lysine residues to surface phospholipids changing their net charge, leading to the repelling of the AMPs. In the present study, we determined that lysX gene is differentially expressed among Mtb strains...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28794178/potential-of-high-affinity-slow-off-rate-modified-aptamer-somamer-reagents-for-mycobacterium-tuberculosis-proteins-as-tools-for-infection-models-and-diagnostic-applications
#6
Theresa Russell, Louis S Green, Taylor Rice, Nicole A Kruh-Garcia, Karen Dobos, Mary A DeGroote, Thomas Hraha, David G Sterling, Nebojsa Janjic, Urs A Ochsner
Direct pathogen detection in blood to diagnose active tuberculosis (TB) has been difficult, due to low levels of circulating antigens or due to the lack of specific, high-affinity binding reagents and reliable assays with adequate sensitivity. We sought to determine whether slow off-rate modified aptamer (SOMAmer) reagents with sub-nanomolar affinity for M. tuberculosis (Mtb) proteins (antigen 85A, 85B, 85C, GroES, GroEL2, DnaK, CFP10, KAD, CFP2, RplL and Tpx) could be useful to diagnose tuberculosis. When incorporated into the multiplexed, array-based proteomic SOMAscan assay, limits of detection reached the sub-picomolar range in 40% serum...
August 9, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28790995/trehalose-polyphleates-external-cell-wall-lipids-in-mycobacterium-abscessus-are-associated-with-the-formation-of-clumps-with-cording-morphology-which-have-been-associated-with-virulence
#7
Marta Llorens-Fons, Míriam Pérez-Trujillo, Esther Julián, Cecilia Brambilla, Fernando Alcaide, Thomas F Byrd, Marina Luquin
Mycobacterium abscessus is a reemerging pathogen that causes pulmonary diseases similar to tuberculosis, which is caused by Mycobacterium tuberculosis. When grown in agar medium, M. abscessus strains generate rough (R) or smooth colonies (S). R morphotypes are more virulent than S morphotypes. In searching for the virulence factors responsible for this difference, R morphotypes have been found to form large aggregates (clumps) that, after being phagocytozed, result in macrophage death. Furthermore, the aggregates released to the extracellular space by damaged macrophages grow, forming unphagocytosable structures that resemble cords...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28783414/guanine-nucleotide-exchange-factor-h1-promotes-inflammatory-cytokine-production-and-intracellular-mycobacterial-elimination-in-macrophages
#8
Hui Wang, Jinli Wang, Jiahui Yang, Xiaofan Yang, Jianchun He, Ruining Wang, Sudong Liu, Lin Zhou, Li Ma
Mycobacterium tuberculosis (M.tb), which causes tuberculosis, is a host-adapted intracellular pathogen that can live within macrophages owning to its ability to arrest phagolysosome biogenesis. The guanine nucleotide exchange factor H1 (GEF-H1) may contribute to the phagocytosis of bacteria by macrophages through mediating the crosstalk between microtubules and the actin cytoskeleton. Its role in Shigella infection has been determined but little is known about the role of GEF-H1 in mycobacterial infection. In the present study, we demonstrated that GEF-H1 functioned as a key regulator of the macrophage-mediated anti-mycobacterial response...
August 7, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28782713/in-vitro-activity-of-alpha-viniferin-isolated-from-the-roots-of-carex-humilis-against-mycobacterium-tuberculosis
#9
Hoonhee Seo, Mijung Kim, Sukyung Kim, Hafij Al Mahmud, Md Imtiazul Islam, Kung-Woo Nam, Myoung-Lae Cho, Hyun-Sook Kwon, Ho-Yeon Song
This study explores the antitubercular activity of α-viniferin, a bioactive phytochemical compound obtained from Carex humilis. α-Viniferin was active against both drug-susceptible and -resistant strains of Mycobacterium tuberculosis at MIC50s of 4.6 μM in culture broth medium and MIC50s of 2.3-4.6 μM inside macrophages and pneumocytes. In combination with streptomycin and ethambutol, α-viniferin exhibited an additive effect and partial synergy, respectively, against M. tuberculosis H37Rv. α-Viniferin also did not show cytotoxicity in any of the cell lines tested up to a concentration of 147 μM, which gives this compound a selectivity index of >32...
August 4, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28768708/identification-of-compounds-that-decrease-numbers-of-mycobacteria-in-human-macrophages-in-the-presence-of-serum-amyloid-p
#10
Wang Xiang, Nehemiah Cox, Richard H Gomer
Mϕs are a heterogeneous population of cells and include classically activated Mϕs (M1) and alternatively activated Mϕs (M2). Mϕs can change from M1 to M2 and vice versa in response to environmental stimuli. Serum amyloid P (SAP) is a constitutive plasma protein that polarizes Mϕs to an M2 phenotype, and part of this effect is mediated through FcγRI receptors. In an effort to find ways to alter Mϕs phenotypes, we screened for compounds that can block the SAP-FcγRI interaction. From a screen of 3000 compounds, we found 12 compounds that reduced the ability of fluorescently labeled human SAP to bind cells expressing human FcγRI...
August 2, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28767693/dendritic-cells-that-phagocytose-apoptotic-macrophages-loaded-with-mycobacterial-antigens-activate-cd8-t-cells-via-cross-presentation
#11
Patricia Espinosa-Cueto, Alejandro Magallanes-Puebla, Carlos Castellanos, Raul Mancilla
While homeostatic apoptosis is immunologically silent, macrophage apoptosis during Mycobacterium tuberculosis infection can potentially induce an immune response against the mycobacteria. To examine the role of dendritic cells in this response, macrophage apoptosis was induced by incubating the macrophage with cell wall extracts of mycobacteria expressing LpqH. The apoptogenic proteins of the cell wall extracts were engulfed by the macrophage and then were translocated from the cytosol to the nuclei of the dying cells...
2017: PloS One
https://www.readbyqxmd.com/read/28754881/sp110-enhances-macrophage-resistance-to-mycobacterium-tuberculosis-via-inducing-endoplasmic-reticulum-stress-and-inhibiting-anti-apoptotic-factors
#12
Yongyan Wu, Zekun Guo, Fayang Liu, Kezhen Yao, Mingqing Gao, Yan Luo, Yong Zhang
Tuberculosis remains a leading health problem worldwide and still accounts for about 1.3 million deaths annually. Expression of the mouse Sp110 nuclear body protein (Sp110) upregulates the apoptotic pathway, which plays an essential role in enhancing host immunity to Mycobacterium tuberculosis (Mtb). However, the mechanism of this upregulation is unclear. Here, we have identified 253 proteins in mouse macrophages that interact with Sp110, of which 251 proteins were previously uncharacterized. The results showed that Sp110 interacts with heat shock protein 5 (Hspa5) to activate endoplasmic reticulum (ER) stress-induced apoptosis, and that this is essential for Sp110 enhanced macrophage resistance to Mtb...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28754681/nitric-oxide-modulates-macrophage-responses-to-mycobacterium-tuberculosis-infection-through-activation-of-hif-1%C3%AE-and-repression-of-nf-%C3%AE%C2%BAb
#13
Jonathan Braverman, Sarah A Stanley
IFN-γ is essential for control of Mycobacterium tuberculosis infection in vitro and in vivo. However, the mechanisms by which IFN-γ controls infection remain only partially understood. One of the crucial IFN-γ target genes required for control of M. tuberculosis is inducible NO synthase (iNOS). Although NO produced by iNOS is thought to have direct bactericidal activity against M. tuberculosis, the role of NO as a signaling molecule has been poorly characterized in the context M. tuberculosis infection. In this study, we found that iNOS broadly regulates the macrophage transcriptome during M...
July 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28748751/update-on-nitazoxanide-a-multifunctional-chemotherapeutic-agent
#14
Anshul Shakya, Hans Raj Bhat, Surjit Kumar Ghosh
Background: The thiazolide nitazoxanide (NTZ) is a broad-spectrum anti-infective drug that adversely affects viability, growth, and proliferation of a range of extracellular and intracellular protozoan, helminths, anaerobic and microaerophilic bacteria, and viruses. Methods: Current review compiled the potential chemotherapeutic efficacy of NTZ against a variety of such disease-causing macro and/or micro-organisms as well as neoplastic cells, using various search engines viz...
July 27, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28747644/active-nuclear-transcriptome-analysis-reveals-inflammasome-dependent-mechanism-for-early-neutrophil-response-to-mycobacterium-marinum
#15
Amy Kenyon, Daria Gavriouchkina, Jernej Zorman, Giorgio Napolitani, Vincenzo Cerundolo, Tatjana Sauka-Spengler
The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and il1β...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28745326/defective-positioning-in-granulomas-but-not-lung-homing-limits-cd4-t-cell-interactions-with-mycobacterium-tuberculosis-infected-macrophages-in-rhesus-macaques
#16
K D Kauffman, M A Sallin, S Sakai, O Kamenyeva, J Kabat, D Weiner, M Sutphin, D Schimel, L Via, C E Barry, T Wilder-Kofie, I Moore, R Moore, D L Barber
Protection against Mycobacterium tuberculosis (Mtb) infection requires CD4 T cells to migrate into the lung and interact with infected macrophages. In mice, less-differentiated CXCR3(+) CD4 T cells migrate into the lung and suppress growth of Mtb, whereas CX3CR1(+) terminally differentiated Th1 cells accumulate in the blood vasculature and do not control pulmonary infection. Here we examine CD4 T-cell differentiation and lung homing during primary Mtb infection of rhesus macaques. Mtb-specific CD4 T cells simultaneously appeared in the airways and blood ∼21-28 days post exposure, indicating that recently primed effectors are quickly recruited into the lungs after entering circulation...
July 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28744015/lactate-oxidation-facilitates-growth-of-mycobacterium-tuberculosis-in-human-macrophages
#17
Sandra Billig, Marie Schneefeld, Claudia Huber, Guntram A Grassl, Wolfgang Eisenreich, Franz-Christoph Bange
Mycobacterium tuberculosis (Mtb) uses alveolar macrophages as primary host cells during infection. In response to an infection, macrophages switch from pyruvate oxidation to reduction of pyruvate into lactate. Lactate might present an additional carbon substrate for Mtb. Here, we demonstrate that Mtb can utilize L-lactate as sole carbon source for in vitro growth. Lactate conversion is strictly dependent on one of two potential L-lactate dehydrogenases. A knock-out mutant lacking lldD2 (Rv1872c) was unable to utilize L-lactate...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743081/mycobacterium-tuberculosis-ppe44-rv2770c-is-involved-in-response-to-multiple-stresses-and-promotes-the-macrophage-expression-of-il-12-p40-and-il-6-via-the-p38-erk-and-nf-%C3%AE%C2%BAb-signaling-axis
#18
Zhaoxiao Yu, Chenhui Zhang, Mingliang Zhou, Qiming Li, Hui Li, Wei Duan, Xue Li, Yonghong Feng, Jianping Xie
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a formidable threat to global public health. The successful intracellular persistence of M. tuberculosis significantly contributes to the intractability of tuberculosis. Proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) are mycobacterial exclusive protein families that widely reported to be involved in the bacterial virulence, physiology and interaction with host. Rv2770c (PPE44), a predicted virulence factor, was up-regulated upon the infected guinea pig lungs...
July 22, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28739828/mice-bone-marrow-sca-1-cd44-mesenchymal-stem-cells-kill-avirulent-mycobacteria-but-not-mycobacterium-tuberculosis-through-modulation-of-cathelicidin-expression-via-p38-mapk-dependent-pathway
#19
Sumanta Kumar Naik, Avinash Padhi, Geetanjali Ganguli, Srabasti Sengupta, Sanghamitra Pati, Dasarathi Das, Avinash Sonawane
Mycobacterium tuberculosis (Mtb) primarily infects lung macrophages. However, recent study has shown that Mtb also infect and persist in dormant form inside the bone marrow mesenchymal stem cells (BM-MSCs) even after successful antibiotic therapy. However, the mechanism(s) by which Mtb survives in BM-MSCs is still not known. Like macrophages, BM-MSCs do not contain a well-defined endocytic pathway, which is known to play a central role in the clearance of internalized mycobacteria. Here, we studied the fate of virulent and avirulent mycobacteria in Sca-1(+)/CD44(+) BM-MSCs...
July 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28728275/-changes-and-differences-of-dna-methylation-in-human-macrophages-infected-with-virulent-and-avirulent-mycobacterium-tuberculosis
#20
L N Lyu, H Y Jia, Z H Li, Z Q Liu, Z D Zhang
Objective: To profile DNA methylation and compare differentially methylated region (DMR) of macrophages infected with virulent and avirulent strains of Mycobacterium tuberculosis (MTB). Methods: PMA(50 ng/ml) treated THP-1 macrophages were left uninfected or infected with the virulent H37Rv(THP-1/Rv) or avirulent H37Ra(THP-1/Ra). The genomic DNA was then extracted and DNA methylation was profiled via Reduced Representation Bisulfite Sequencing (RRBS). The DNA methylation pattern and DMRs between the tested samples were indentified...
July 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
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