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https://www.readbyqxmd.com/read/28226776/an-in-silico-model-of-the-effects-of-vitamin-d3-on-mycobacterium-infected-macrophage
#1
Maya Gough, Elebeoba May, Maya Gough, Elebeoba May, 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/28225907/characterisation-of-iunh-gene-knockout-strain-from-mycobacterium-tuberculosis
#2
Anne Drumond Villela, Valnês da Silva Rodrigues, Antônio Frederico Michel Pinto, Priscila Lamb Wink, Zilpa Adriana Sánchez-Quitian, Guilherme Oliveira Petersen, Maria Martha Campos, Luiz Augusto Basso, Diógenes Santiago Santos
BACKGROUND: Tuberculosis (TB) is an infectious disease caused mainly by the bacillus Mycobacterium tuberculosis. The better understanding of important metabolic pathways from M. tuberculosis can contribute to the development of novel therapeutic and prophylactic strategies to combat TB. Nucleoside hydrolase (MtIAGU-NH), encoded by iunH gene (Rv3393), is an enzyme from purine salvage pathway in M. tuberculosis. MtIAGU-NH accepts inosine, adenosine, guanosine, and uridine as substrates, which may point to a pivotal metabolic role...
March 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28225337/multiple-cytokines-for-the-detection-of-mycobacterium-tuberculosis-infection-in-children-with-tuberculosis
#3
N Nausch, C Lundtoft, G Schulz, H Henckel, E Mayatepek, B Fleischer, F M Marx, M Jacobsen
SETTING: Interferon-gamma (IFN-γ) release assays (IGRAs) play an important role in the diagnosis of Mycobacterium tuberculosis infection. However, in children with tuberculosis (TB), some studies have shown increased frequencies of false-negative or indeterminate IGRA results. OBJECTIVE: To analyse the spectrum of different cytokines to improve the diagnostic accuracy of IGRAs in latent tuberculous infection (LTBI) and active TB. DESIGN: We performed multiplex cytokine expression analysis of QuantiFERON® Gold In-Tube supernatants in children with active TB (n = 21) and disease-free contacts with (n = 15) and without LTBI (n = 12), to determine the sensitivity and specificity of the modified tests...
March 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28223969/mycobacterium-tuberculosis-prolyl-oligopeptidase-induces-in-vitro-secretion-of-proinflammatory-cytokines-by-peritoneal-macrophages
#4
Brina Portugal, Flávia N Motta, Andre F Correa, Diego O Nolasco, Hugo de Almeida, Kelly G Magalhães, Ana L V Atta, Francisco D Vieira, Izabela M D Bastos, Jaime M Santana
Tuberculosis (TB) is a disease that leads to death over 1 million people per year worldwide and the biological mediators of this pathology are poorly established, preventing the implementation of effective therapies to improve outcomes in TB. Host-bacterium interaction is a key step to TB establishment and the proteases produced by these microorganisms seem to facilitate bacteria invasion, migration and host immune response evasion. We presented, for the first time, the identification, biochemical characterization, molecular dynamics (MDs) and immunomodulatory properties of a prolyl oligopeptidase (POP) from Mycobacterium tuberculosis (POPMt)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28215633/tlr-4-mirna-32-5p-fstl1-signaling-regulates-mycobacterial-survival-and-inflammatory-responses-in-mycobacterium-tuberculosis-infected-macrophages
#5
Zhi-Min Zhang, Ai-Rong Zhang, Min Xu, Jun Lou, Wei-Qiang Qiu
Macrophages play a pivotal role in host immune response against mycobacterial infection, which is tightly modulated by multiple factors, including microRNAs. The purpose of the present study was to investigate the biological function and potential mechanism of miR-32-5p in human macrophages during Mycobacterium tuberculosis (M.tb) infection. The results demonstrated that miR-32-5p was robustly enhanced in THP-1 and U937 cells in response to M.tb infection. TLR-4 signaling was required for upregulation of miR-32-5p induced by M...
February 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28209712/mycobacterium-tuberculosis-esxl-inhibit-mhc-ii-expression-by-promoting-hypermethylation-in-class-ii-transactivator-loci-in-macrophages
#6
Srabasti Sengupta, Saba Naz, Ishani Das, Abdul Ahad, Avinash Padhi, Sumanta Naik, Geetanjali Ganguli, Kaliprasad Patnaik, Sunil Kumar Raghav, Vinay Nandicoori, Avinash Sonawane
Mycobacterium tuberculosis (Mtb) is known to modulate the host immune responses to facilitate its persistence inside the host cells. One of the key mechanisms includes repression of class-II transactivator (CIITA) and MHC-II expression in infected macrophages. However, the precise mechanism of CIITA and MHC-II down-regulation is not well studied. Mtb 6-kDa early secretory antigenic target (ESAT-6) is a known potent virulence and antigenic determinant. Mtb genome encodes 23 such ESAT-6 family proteins. We herein report that Mtb and M...
February 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28206680/an-ssdna-aptamer-against-mannose-capped-lipoarabinomannan-enhances-anti-tuberculosis-activity-of-macrophages-through-downregulation-of-lipid-sensing-nuclear-receptor-peroxisome-proliferator-activated-receptor-%C3%AE-expression
#7
Qin Pan, Jiamin Yan, Qi Liu, Chunhui Yuan, Xiao-Lian Zhang
Mannose-capped lipoarabinomannan (ManLAM) is an immunomodulatory epitope of Mycobacterium tuberculosis (Mtb). We previously generated an aptamer (ZXL1) that specifically binds to ManLAM from the virulent Mtb H37Rv strain and reported that ZXL1 functioned as an antagonist, inhibiting the ManLAM-induced immunosuppression of dendritic cells (DCs). In the present study, we found that ZXL1 inhibited Mtb entry into murine macrophages. ZXL1 enhanced IL-1β and IL-12 mRNA expression and cytokine production in ManLAM-treated macrophages but decreased IL-10 production...
February 16, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28205097/identifying-and-characterising-ppe7-rv0354c-high-activity-binding-peptides-and-their-role-in-inhibiting-cell-invasion
#8
Diana P Díaz, Marisol Ocampo, Yahson Varela, Hernando Curtidor, Manuel A Patarroyo, Manuel E Patarroyo
This study was aimed at characterising the PPE7 protein from the PE/PPE protein family. The presence and transcription of the rv0354c gene in the Mycobacterium tuberculosis complex was determined and the subcellular localisation of the PPE7 protein on mycobacterial membrane was confirmed by immunoelectron microscope. Two peptides were identified as having high binding activity (HABPs) and were tested in vitro regarding the invasion of Mycobacterium tuberculosis H37Rv. HABP 39224 inhibited invasion in A549 epithelial cells and U937 macrophages by more than 50%, whilst HABP 39225 inhibited invasion by 40% in U937 cells...
February 15, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28203237/activation-of-the-wnt-pathway-by-mycobacterium-tuberculosis-a-wnt-wnt-situation
#9
REVIEW
Tomás Villaseñor, Edgardo Madrid-Paulino, Rafael Maldonado-Bravo, Antonio Urbán-Aragón, Leonor Pérez-Martínez, Gustavo Pedraza-Alva
Mycobacterium tuberculosis (M. tuberculosis), an intracellular pathogenic Gram-positive bacterium, is the cause of tuberculosis (TB), a major worldwide human infectious disease. The innate immune system is the first host defense against M. tuberculosis. The recognition of this pathogen is mediated by several classes of pattern recognition receptors expressed on the host innate immune cells, including Toll-like receptors, Nod-like receptors, and C-type lectin receptors like Dectin-1, the Mannose receptor, and DC-SIGN...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28199374/a-novel-mycobacterial-in-vitro-infection-assay-identifies-differences-of-induced-macrophage-apoptosis-between-cd4-and-cd8-t-cells
#10
Vanesa Nkwouano, Sven Witkowski, Nidja Rehberg, Rainer Kalscheuer, Norman Nausch, Ertan Mayatepek, Marc Jacobsen
Macrophages are natural host cells for pathogenic mycobacteria, like Mycobacterium tuberculosis (M.tb). Immune surveillance by T cells and interaction with M.tb infected macrophages is crucial for protection against M.tb reactivation and development of active tuberculosis. Several factors play a role in the control of M.tb infection but reliable biomarkers remain elusive. One major obstacle is the absence of functional in vitro assays which allow concomitant determination of i) mycobacterial eradication; ii) cytotoxic effects on host macrophages; and iii) effector T-cell functions...
2017: PloS One
https://www.readbyqxmd.com/read/28198348/down-regulation-of-pe11-a-cell-wall-associated-esterase-enhances-the-biofilm-growth-of-mycobacterium-tuberculosis-and-reduces-cell-wall-virulence-lipid-levels
#11
Shivangi Rastogi, Amit Kumar Singh, Garima Pant, Kalyan Mitra, Koneni V Sashidhara, Manju Y Krishnan
PE11 (Rv1169c or LipX) is a cell wall associated esterase/lipase of Mycobacterium tuberculosis (Mtb). Evidences suggest that PE11 is expressed by Mtb both in vitro and in vivo. Previous studies have shown that PE11 leads to modification in cell wall lipid content and enhanced virulence when expressed in the non-pathogenic surrogate Mycobacterium smegmatis. Since cell wall lipids often play different roles in pathogenic and non-pathogenic mycobacteria, we investigated the role of PE11 in its host, Mtb. Mtb with lowered expression of PE11 (PE11 knock-down) displayed significant changes in colony morphology and cell wall lipid profile, confirming the role of PE11 in cell wall architecture...
January 2017: Microbiology
https://www.readbyqxmd.com/read/28193630/mycolates-of-mycobacterium-tuberculosis-modulate-the-flow-of-cholesterol-for-bacillary-proliferation-in-murine-macrophages
#12
Ilke Vermeulen, Mark Baird, Juma Al-Dulayymi, Muriel Smet, Jan Verschoor, Johan Grooten
The differentiation of macrophages into lipid-filled foam cells is a hallmark of the lung granuloma that forms in patients with active tuberculosis (TB). Mycolic acids (MAs), the abundant lipid virulence factors in the cell wall of Mycobacterium tuberculosis (Mtb), can induce this foam phenotype possibly as a way to perturb host cell lipid homeostasis to support the infection. It is not exactly clear how MAs allow differentiation of foam cells during Mtb infection. Here we investigated how chemically synthetic MAs, each with a defined stereochemistry similar to natural Mtb-associated mycolates, influence cell foamy phenotype and mycobacterial proliferation in murine host macrophages...
February 13, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28192437/species-dependent-impact-of-helminth-derived-antigens-on-human-macrophages-infected-with-mycobacterium-tuberculosis-direct-effect-on-the-innate-anti-mycobacterial-response
#13
Naomi Aira, Anna-Maria Andersson, Susmita K Singh, Derek M McKay, Robert Blomgran
BACKGROUND: In countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. While Mycobacterium tuberculosis (Mtb) gives rise to a pro-inflammatory Th1 response, a Th2 response is typical of helminth infections. A strong Th2 response has been associated with decreased protection against tuberculosis. PRINCIPAL FINDINGS: We investigated the direct effect of helminth-derived antigens on human macrophages, hypothesizing that helminths would render macrophages less capable of controlling Mtb...
February 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28192419/seq-well-portable-low-cost-rna-sequencing-of-single-cells-at-high-throughput
#14
Todd M Gierahn, Marc H Wadsworth, Travis K Hughes, Bryan D Bryson, Andrew Butler, Rahul Satija, Sarah Fortune, J Christopher Love, Alex K Shalek
Single-cell RNA-seq can precisely resolve cellular states, but applying this method to low-input samples is challenging. Here, we present Seq-Well, a portable, low-cost platform for massively parallel single-cell RNA-seq. Barcoded mRNA capture beads and single cells are sealed in an array of subnanoliter wells using a semipermeable membrane, enabling efficient cell lysis and transcript capture. We use Seq-Well to profile thousands of primary human macrophages exposed to Mycobacterium tuberculosis.
February 13, 2017: Nature Methods
https://www.readbyqxmd.com/read/28178208/effector-mechanisms-of-neutrophils-within-the-innate-immune-system-in-response-to-mycobacterium-tuberculosis-infection
#15
REVIEW
Eric Warren, Garrett Teskey, Vishwanath Venketaraman
Neutrophils have a significant yet controversial role in the innate immune response to Mycobacterium tuberculosis (M. tb) infection, which is not yet fully understood. In addition to neutrophils' well-known effector mechanisms, they may also help control infection of M. tb through the formation of neutrophil extracellular traps (NETs), which are thought to further promote the killing of M. tb by resident alveolar macrophages. Cytokines such as IFN-γ have now been shown to serve an immunomodulatory role in neutrophil functioning in conjunction to its pro-inflammatory function...
February 7, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28176867/primary-macrophages-and-j774-cells-respond-differently-to-infection-with-mycobacterium-tuberculosis
#16
Nuria Andreu, Jody Phelan, Paola F de Sessions, Jacqueline M Cliff, Taane G Clark, Martin L Hibberd
Macrophages play an essential role in the early immune response to Mycobacterium tuberculosis and are the cell type preferentially infected in vivo. Primary macrophages and macrophage-like cell lines are commonly used as infection models, although the physiological relevance of cell lines, particularly for host-pathogen interaction studies, is debatable. Here we use high-throughput RNA-sequencing to analyse transcriptome dynamics of two macrophage models in response to M. tuberculosis infection. Specifically, we study the early response of bone marrow-derived mouse macrophages and cell line J774 to infection with live and γ-irradiated (killed) M...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28176854/mycobacterium-tuberculosis-exploits-the-ppm1a-signaling-pathway-to-block-host-macrophage-apoptosis
#17
Kaitlyn Schaaf, Samuel R Smith, Alexandra Duverger, Frederic Wagner, Frank Wolschendorf, Andrew O Westfall, Olaf Kutsch, Jim Sun
The ability to suppress host macrophage apoptosis is essential for M. tuberculosis (Mtb) to replicate intracellularly while protecting it from antibiotic treatment. We recently described that Mtb infection upregulated expression of the host phosphatase PPM1A, which impairs the antibacterial response of macrophages. Here we establish PPM1A as a checkpoint target used by Mtb to suppress macrophage apoptosis. Overproduction of PPM1A suppressed apoptosis of Mtb-infected macrophages by a mechanism that involves inactivation of the c-Jun N-terminal kinase (JNK)...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174296/ncs1-regulates-ca2-dependent-focal-exocytosis-of-golgi-derived-vesicles-to-help-phagocytic-uptake-in-macrophages
#18
Nimi Vashi, Syed Bilal Ahmad Andrabi, Swapnil Ghanwat, Mrutyunjay Suar, Dhiraj Kumar
During phagocytic uptake by macrophages, role of Golgi apparatus was previously ruled out. Notably all such reports were limited to Fcγ-receptor mediated phagocytosis. Here we unravel a highly devolved mechanism for recruitment of Golgi-derived secretory vesicles during phagosome biogenesis, which was important for uptake of most cargos except IgG-coated ones. We report recruitment of Mannosidase-II positive Golgi-derived vesicles during uptake of diverse targets including latex beads, E. coli, Salmonella Typhimurium and Mycobacterium tuberculosis in human and mouse macrophages...
February 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28169347/attenuation-of-lymphocyte-immune-responses-during-mycobacterium-avium-complex-induced-lung-disease-due-to-increasing-expression-of-programmed-death-1-on-lymphocytes
#19
Chin-Chung Shu, Jann-Yuan Wang, Ming-Fang Wu, Chen-Tu Wu, Hsin-Chih Lai, Li-Na Lee, Bor-Luen Chiang, Chong-Jen Yu
Mycobacterium avium complex-induced lung disease (MAC-LD) becomes important due to its increasing prevalence. Attenuated cellular immunity associated with programmed cell death (PD)-1 may play a pathophysiological role in MAC-LD but lacks of investigation. We enrolled 80 participants in this prospective study, including 50 with MAC-LD and 30 healthy controls. Peripheral blood mononuclear cells (PBMCs), lymphocytes and monocyte-derived macrophages were used for MAC antigen stimulation. Patients with MAC-LD had lower tumor necrosis factor-α and interferon-γ responses compared to the healthy controls in PBMC stimulation assays with MAC bacilli...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167548/ga-iii-nanoparticles-inhibit-growth-of-both-tb-and-hiv-and-release-of-il-6-and-il-8-in-co-infected-macrophages
#20
Seoung-Ryoung Choi, Bradley E Britigan, Prabagaran Narayanasamy
Treatment of individuals co-infected with human immunodeficiency virus-1 (HIV) and Mycobacterium tuberculosis (M.tb) is challenging due to prolonged treatment requirements, drug toxicity and emergence of drug resistance. Mononuclear phagocytes (MP; macrophages) are one of the natural reservoirs for both HIV and M.tb Here, the treatment of HIV and M.tb co-infection was studied by preloading human macrophages with MP-targeted gallium (Ga) nanoparticles to limit subsequent simultaneous infection with both HIV and M...
February 6, 2017: Antimicrobial Agents and Chemotherapy
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