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macrophage tuberculosis

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https://www.readbyqxmd.com/read/28442574/the-r753q-polymorphism-in-toll-like-receptor-2-tlr2-attenuates-innate-immune-responses-to-mycobacteria-and-impairs-myd88-adapter-recruitment-to-tlr2
#1
Goutham Pattabiraman, Rahul Panchal, Andrei E Medvedev
Toll-like receptor (TLR) 2 plays a critical role in host defenses against mycobacterial infections. The Arg753Gln (R753Q) TLR2 polymorphism has been associated with increased incidence of tuberculosis and infections with non-tuberculous mycobacteria in human populations, but the mechanisms by which this polymorphism affects TLR2 signaling are unclear. In this study, we determined the impact of the R753Q TLR2 polymorphism on macrophage sensing of Mycobacterium smegmatis. Upon infection with M. smegmatis, macrophages from knock-in (KI) mice harboring R753Q TLR2 expressed lower levels of TNF-α, IL-1β, IL-6 and IL-10 compared to cells from wild-type (WT) mice but both R753Q TLR2 and WT mice exhibited comparable bacterial burdens...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28440335/mycobacterium-tuberculosis-pe_pgrs41-enhances-the-intracellular-survival-of-m-smegmatis-within-macrophages-via-blocking-innate-immunity-and-inhibition-of-host-defense
#2
Wanyan Deng, Quanxin Long, Jie Zeng, Ping Li, Wenmin Yang, Xinchun Chen, Jianping Xie
The success of Mycobacterium tuberculosis (M. tuberculosis) as a pathogen is largely contributes to its ability to manipulate the host immune responses. The genome of M. tuberculosis encodes multiple immune-modulatory proteins, including several members of the multi-genic PE_PPE family. Despite of intense research, the roles of PE_PGRS proteins in mycobacterial pathogenesis remain elusive. The function of M. tuberculosis PE_PGRS41, characterized by an extended and unique C-terminal domain, was studied. Expression of PE_PGRS41 in Mycobacterium smegmatis, a non-pathogenic species intrinsically deficient of PE_PGRS, severely impaired the resistance of the recombinant to multiple stresses via altering the cell wall integrity...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436453/functional-thermodynamics-structural-and-biological-studies-of-in-silico-identified-inhibitors-of-mycobacterium-tuberculosis-enoyl-acp-coa-reductase-enzyme
#3
Leonardo K B Martinelli, Mariane Rotta, Anne D Villela, Valnês S Rodrigues-Junior, Bruno L Abbadi, Rogério V Trindade, Guilherme O Petersen, Giuliano M Danesi, Laura R Nery, Ivani Pauli, Maria M Campos, Carla D Bonan, Osmar Norberto de Souza, Luiz A Basso, Diogenes S Santos
Novel chemotherapeutics agents are needed to kill Mycobacterium tuberculosis, the main causative agent of tuberculosis (TB). The M. tuberculosis 2-trans-enoyl-ACP(CoA) reductase enzyme (MtInhA) is the druggable bona fide target of isoniazid. New chemotypes were previously identified by two in silico approaches as potential ligands to MtInhA. The inhibition mode was determined by steady-state kinetics for seven compounds that inhibited MtInhA activity. Dissociation constant values at different temperatures were determined by protein fluorescence spectroscopy...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28435012/il-10-down-regulates-the-expression-of-survival-associated-gene-hspx-of-mycobacterium-tuberculosis-in-murine-macrophage
#4
Babban Jee, Pawan Sharma, Kiran Katoch, Beenu Joshi, Sudhir Kumar Awasthi
Mycobacterium tuberculosis (MTB) adopts a special survival strategy to overcome the killing mechanism(s) of host immune system. Amongst the many known factors, small heat shock protein 16.3 (sHSP16.3) of MTB encoded by gene hspX has been reported to be critical for the survival of MTB. In the present study, the effect of recombinant murine interferon-gamma (rmIFN-γ) and recombinant murine interleukin-10 (rmIL-10) on the expression of gene hspX of MTB in murine macrophage RAW264.7 has been investigated. By real-time RT-PCR, it was observed that three increasing concentrations (5, 25 and 50ng/ml) of rmIFN-γ significantly up-regulated the expression of hspX whereas similar concentrations of rmIL-10 (5, 25 and 50ng/ml) significantly down-regulated the hspX expression...
April 20, 2017: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28428627/glucocorticoids-suppress-antimicrobial-autophagy-and-nitric-oxide-production-and-facilitate-mycobacterial-survival-in-macrophages
#5
Jinli Wang, Ruining Wang, Hui Wang, Xiaofan Yang, Jiahui Yang, Wenjing Xiong, Qian Wen, Li Ma
Chronic administration of glucocorticoids has been shown to render individuals highly susceptible to mycobacterial infection and lead to reactivation of latent bacilli. However, the effect of glucocorticoids on innate anti-mycobacterial defense, especially in macrophages remains largely unknown. Here, we found that glucocorticoids inhibited the innate immune response, antimicrobial nitric oxide production and autophagy in mycobacteria-challenged macrophages. Meanwhile, maturation and acidification of mycobacterial phagosomes were attenuated in RAW264...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424703/immune-responses-to-bacillus-calmette-gu%C3%A3-rin-vaccination-why-do-they-fail-to-protect-against-mycobacterium-tuberculosis
#6
REVIEW
Juan I Moliva, Joanne Turner, Jordi B Torrelles
Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB), is the current leading cause of death due to a single infectious organism. Although curable, the broad emergence of multi-, extensive-, extreme-, and total-drug resistant strains of M.tb has hindered eradication efforts of this pathogen. Furthermore, computational models predict a quarter of the world's population is infected with M.tb in a latent state, effectively serving as the largest reservoir for any human pathogen with the ability to cause significant morbidity and mortality...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28419514/activition-of-tlr7-inhibition-of-mycobacterium-tuberculosis-survival-by-autophagy-in-raw-264-7-macrophages
#7
Meng Bao, Zhengjun Yi, Yurong Fu
The aim of the study was to evaluate the effect of regulation of TLR7 on Mycobacterium tuberculosis (Mtb) survival in macrophages. TLR7 expression in macrophages infected by Mtb was detected by RT-PCR and western blotting. Regulation of TLR7 was achieved by single strand RNA (ssRNA) or siRNA. The effects of TLR7 on Mtb survival and cell viability were detected by acid fast staining and cell counting kit-8, respectively. Cell ultrastructure was observed via transmission electron microscopy (TEM), and autophagy related protein LC3 was analyzed by western blotting...
April 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28416555/mycobacterium-tuberculosis-proteome-response-to-anti-tuberculosis-compounds-reveals-metabolic-escape-pathways-that-prolong-bacterial-survival
#8
Lia Danelishvili, Natalia Shulzhenko, Jessica J J Chinison, Lmar Babrak, Jialu Hu, Andriy Morgun, Gregory Burrows, Luiz E Bermudez
Tuberculosis (TB) continues to be one of the most common bacterial infectious diseases and the leading cause of death in many parts of the world. A major limitation of TB therapy is slow killing of infecting organism, increasing the risk for the development of tolerance phenotype and drug-resistance. Studies indicate that M. tuberculosis (Mtb) takes several days to be killed upon treatment with lethal concentrations of antibiotics both in vitro and in vivo To investigate how metabolic remodeling can enable transient bacterial survival during exposure with bactericidal concentrations of compounds, Mtb H37Rv strain was exposed to twice of the minimal inhibitory concentration of isoniazid, rifampicin, moxifloxacin, mefloquine or bedaquiline for 24h, 48h, 4 days, and 6 days, and the bacterial proteomic response was analyzed using the quantitative shotgun mass spectrometry...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28412202/the-immunosuppressive-effects-of-a-novel-recombinant-lipq-rv2485c-protein-of-mycobacterium-tuberculosis-on-human-macrophage-cell-lines
#9
Anjani Kumar, Manisha, Gurkamaljit Kaur Sangha, Anju Shrivastava, Jagdeep Kaur
Mycobacterium tuberculosis (MTB), an intracellular pathogen, still represents a major global health challenge. A number of mycobacterial macromolecules have been shown to target biological processes within host macrophages; however, the exact mechanism for the majority of these host pathogen interactions is still poorly understood. Moreover, the lipid metabolic pathway is one of the most important physiologic pathways that plays a vital role in the survival and infection of Mycobacterium tuberculosis. In present study, we investigated the effect of rLipQ from Mycobacterium tuberculosis H37Rv on macrophage functions in vitro...
April 12, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28401933/bcl-xl-mediates-ripk3-dependent-necrosis-in-m-tuberculosis-infected-macrophages
#10
X Zhao, N Khan, H Gan, F Tzelepis, T Nishimura, S-Y Park, M Divangahi, H G Remold
Virulent Mycobacterium tuberculosis (Mtb) triggers necrosis in host Mϕ, which is essential for successful pathogenesis in tuberculosis. Here we demonstrate that necrosis of Mtb-infected Mϕ is dependent on the action of the cytosolic Receptor Interacting Protein Kinase 3 (RIPK3) and the mitochondrial Bcl-2 family member protein B-cell lymphoma-extra large (Bcl-xL). RIPK3-deficient Mϕ are able to better control bacterial growth in vitro and in vivo. Mechanistically, cytosolic RIPK3 translocates to the mitochondria where it promotes necrosis and blocks caspase 8-activation and apoptosis via Bcl-xL...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28400772/sphingolipids-are-dual-specific-drug-targets-for-the-management-of-pulmonary-infections-perspective
#11
REVIEW
Lalita Sharma, Hridayesh Prakash
Sphingolipids are the major constituent of the mucus secreted by the cells of epithelial linings of lungs where they maintain the barrier functions and prevent microbial invasion. Sphingolipids are interconvertible, and their primary and secondary metabolites have both structural and functional roles. Out of several sphingolipid metabolites, sphingosine-1 phosphate (S1P) and ceramide are central molecules and decisive for sphingolipid signaling. These are produced by enzymatic activity of sphingosine kinase-1 (SK-1) upon the challenge with either biological or physiological stresses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28398760/nicotine-impairs-macrophage-control-of-mycobacterium-tuberculosis
#12
Xiyuan Bai, Jerry A Stitzel, An Bai, Cristian A Zambrano, Matthew Phillips, Philippa Marrack, Edward D Chan
Pure nicotine impairs macrophage killing of Mycobacterium tuberculosis (MTB) but it is not known whether the nicotine component in cigarette smoke (CS) plays a role. Moreover, the mechanisms by which nicotine impairs macrophage immunity against MTB have not been explored. To neutralize the effects of nicotine in CS extract, we utilized a competitive inhibitor to the nicotinic acetylcholine receptor (nAChR) - mecamylamine - as well as macrophages derived from mice with genetic disruption of specific subunits of nAChR...
April 11, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28396657/the-activity-of-a-hexameric-m17-metallo-aminopeptidase-is-associated-with-survival-of-mycobacterium-tuberculosis
#13
Andre F Correa, Izabela M D Bastos, David Neves, Andre Kipnis, Ana P Junqueira-Kipnis, Jaime M de Santana
Mycobacterium tuberculosis is one of the most prevalent human pathogens causing millions of deaths in the last years. Moreover, tuberculosis (TB) treatment has become increasingly challenging owing to the emergence of multidrug resistant M. tuberculosis strains. Thus, there is an immediate need for the development of new anti-TB drugs. Proteases appear to be a promising approach and may lead to shortened and effective treatments for drug-resistant TB. Although the M. tuberculosis genome predicts more than 100 genes encoding proteases, only a few of them have been studied...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28396391/enhanced-respiration-prevents-drug-tolerance-and-drug-resistance-in-mycobacterium-tuberculosis
#14
Catherine Vilchèze, Travis Hartman, Brian Weinrick, Paras Jain, Torin R Weisbrod, Lawrence W Leung, Joel S Freundlich, William R Jacobs
Persistence, manifested as drug tolerance, represents a significant obstacle to global tuberculosis control. The bactericidal drugs isoniazid and rifampicin kill greater than 99% of exponentially growing Mycobacterium tuberculosis (Mtb) cells, but the remaining cells are persisters, cells with decreased metabolic rate, refractory to killing by these drugs, and able to generate drug-resistant mutants. We discovered that the combination of cysteine or other small thiols with either isoniazid or rifampicin prevents the formation of drug-tolerant and drug-resistant cells in Mtb cultures...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28393919/association-of-c-type-lectin-mincle-with-fc%C3%AE%C2%B5ri%C3%AE-%C3%AE-subunits-leads-to-functional-activation-of-rbl-2h3-cells-through-syk
#15
Chisato Honjoh, Kazuyasu Chihara, Hatsumi Yoshiki, Shota Yamauchi, Kenji Takeuchi, Yuji Kato, Yukio Hida, Tamotsu Ishizuka, Kiyonao Sada
Macrophage-inducible C-type lectin (Mincle) interacts with the γ-subunit of high-affinity IgE receptor (FcεRIγ) and activates Syk by recognizing its specific ligand, trehalose-6,6'-dimycolate, a glycolipid produced by Mycobacterium tuberculosis. It has been suggested that mast cells participate in the immune defense against pathogenic microbes including M. tuberculosis, although the functions are still uncertain. In this study, we examined the Mincle-mediated signaling pathway and cellular responses using RBL-2H3 cells...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28391709/immune-modulation-properties-of-herbal-plant-leaves-phyllanthus-niruri-aqueous-extract-on-immune-cells-of-tuberculosis-patient-in-vitro-study
#16
Denise Utami Putri, Ning Rintiswati, Marsetyawan Hne Soesatyo, Sofia Mubarika Haryana
Disease progression in Tuberculosis (TB) is dependent on host's immune system. Phyllanthus niruri, a traditional herb, has long been used to boost immune system in Indonesian society. This study aimed to observe the potential role of P. niruri in inducing immune cells activity in TB patients by in vitro approach. Peripheral blood mononuclear cells (PBMCs) and macrophages were collected from active pulmonary TB patients. After stimulation with graded doses of P. niruri aqueous extract, cell proliferation, phagocytic activity and nitric oxide (NO) release were analysed...
April 10, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28384546/in%C3%A2-vitro-biological-evaluation-of-new-antimycobacterial-salicylanilide-tuftsin-conjugates
#17
Zsuzsa Baranyai, Martin Krátký, Rudolf Vosátka, Eleonóra Szabó, Zsuzsanna Senoner, Sándor Dávid, Jiřina Stolaříková, Jarmila Vinšová, Szilvia Bősze
Tuberculosis is caused by Mycobacterium tuberculosis, an intracellular pathogen that can survive in host cells, mainly in macrophages. An increase of multidrug-resistant tuberculosis qualifies this infectious disease as a major public health problem worldwide. The cellular uptake of the antimycobacterial agents by infected host cells is limited. Our approach is to enhance the cellular uptake of the antituberculars by target cell-directed delivery using drug-peptide conjugates to achieve an increased intracellular efficacy...
March 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28384255/trehalose-dimycolate-interferes-with-fc%C3%AE-r-mediated-phagosome-maturation-through-mincle-shp-1-and-fc%C3%AE-riib-signalling
#18
Emmanuel C Patin, Anna C Geffken, Sam Willcocks, Christoph Leschczyk, Albert Haas, Falk Nimmerjahn, Roland Lang, Theresa H Ward, Ulrich E Schaible
The causative agent of tuberculosis, Mycobacterium tuberculosis (M. tuberculosis), contains an abundant cell wall glycolipid and a crucial virulence factor, trehalose-6,6'-dimycolate (TDM). TDM causes delay of phagosome maturation and thus promotes survival of mycobacteria inside host macrophages by a not fully understood mechanism. TDM signals through the Monocyte-INducible C-type LEctin (Mincle), a recently identified pattern recognition receptor. Here we show that recruitment of Mincle by TDM coupled to immunoglobulin (Ig)G-opsonised beads during Fcγ receptor (FcγR)-mediated phagocytosis interferes with phagosome maturation...
2017: PloS One
https://www.readbyqxmd.com/read/28382943/badger-macrophages-fail-to-produce-nitric-oxide-a-key-anti-mycobacterial-effector-molecule
#19
Kirstin Bilham, Amy C Boyd, Stephen G Preston, Christina D Buesching, Chris Newman, David W Macdonald, Adrian L Smith
The European badger is recognised as a wildlife reservoir for bovine tuberculosis (bTB); the control of which is complex, costly and controversial. Despite the importance of badgers in bTB and the well-documented role for macrophages as anti-mycobacterial effector cells, badger macrophage (bdMφ) responses remain uncharacterised. Here, we demonstrate that bdMφ fail to produce nitric oxide (NO) or upregulate inducible nitric oxide synthase (iNOS) mRNA following Toll-like receptor (TLR) agonist treatment. BdMφ also failed to make NO after stimulation with recombinant badger interferon gamma (bdIFNγ) or a combination of bdIFNγ and lipopolysaccharide...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28380256/investigation-of-the-mycobacterial-enzyme-hsad-as-a-potential-novel-target-for-anti-tubercular-agents-using-a-fragment-based-drug-design-approach
#20
Ali Ryan, Elena Polycarpou, Nathan A Lack, Dimitrios Evangelopoulos, Christian Sieg, Alice Halman, Sanjib Bhakta, Olga Eleftheriadou, Timothy D McHugh, Sebastian Keany, Edward D Lowe, Romain Ballet, Areej Abuhammad, William R Jacobs, Alessio Ciulli, Edith Sim
BACKGROUND AND PURPOSE: With the emergence of extensively drug-resistant tuberculosis there is a need for new anti-tubercular drugs that work through novel mechanisms of action. The meta cleavage product hydrolase, HsaD, has been demonstrated to be critical to the survival of Mycobacterium tuberculosis in macrophages and is encoded in an operon involved in cholesterol catabolism, which is identical in M. tuberculosis and M. bovis BCG. EXPERIMENTAL APPROACH: We generated a mutant strain of M...
April 5, 2017: British Journal of Pharmacology
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