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macrophages tuberculosis

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https://www.readbyqxmd.com/read/30515134/selective-targeting-of-4so-4-n-acetyl-galactosamine-functionalized-mycobacterium-tuberculosis-protein-loaded-chitosan-nanoparticle-to-macrophages-correlation-with-activation-of-immune-system
#1
Nida Mubin, Mohd Saad Umar, Swaleha Zubair, Mohammad Owais
In the present study, we investigated potential of chitosan-based nanoparticles (CNPs) to deliver loaded therapeutic molecules to pathogen harboring macrophages. We fabricated stable CNPs employing ionic cross-linking method and evaluated their potential to target RAW 264.7 cells. The physicochemical characterization of as-synthesized CNPs was determined using electron microscopy, infrared microscopy and zeta potential measurement. Next, cellular uptake and intracellular localization studies of CNPs were followed in living RAW264...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/30514519/cell-death-at-the-cross-roads-of-host-pathogen-interaction-in-mycobacterium-tuberculosis-infection
#2
REVIEW
Krishnaveni Mohareer, Suman Asalla, Sharmistha Banerjee
Tuberculosis (TB) continues to be the leading cause of death by any single infectious agent, accounting for around 1.7 million annual deaths globally, despite several interventions and support programs by national and international agencies. With the development of drug resistance in Mycobacterium tuberculosis (M. tb), there has been a paradigm shift in TB research towards host-directed therapy. The potential targets include the interactions between host and bacterial proteins that are crucial for pathogenesis...
December 2018: Tuberculosis
https://www.readbyqxmd.com/read/30514517/polysaccharide-rich-extract-pre-from-tinospora-cordifolia-inhibits-the-intracellular-survival-of-drug-resistant-strains-of-mycobacterium-tuberculosis-in-macrophages-by-nitric-oxide-induction
#3
Pramod Kumar Gupta, Savita Kulkarni
Plethora of clinical and scientific information obtained in recent past has strengthened the idea that targeting critical constituents of host immune system may have beneficial outcomes for the treatment of tuberculosis. Macrophages being the primary host for Mycobacterium tuberculosis, offer an attractive target for modulation. Owing to their negligible toxicity, plant derived polysaccharides with the ability to activate macrophages; are suitable candidates for immunomodulation. In the present study, effects of polysaccharide rich extract (PRE) isolated from Tinospora cordifolia, on the survival of intracellular MTB strains and activation of macrophages were investigated...
December 2018: Tuberculosis
https://www.readbyqxmd.com/read/30514511/uncloaking-an-ancient-adversary-can-pathogen-biomarker-elicitors-play-a-role-in-confirming-extrapulmonary-tb-and-latent-tb-infection
#4
REVIEW
Brad W Porter, Thara K Venkatappa
Latent tuberculosis infection (LTBI) is diagnosed immunologically using the Mantoux tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). While widely used, immunodiagnostics can produce false negative or false positive results. Pathogen biomarkers provide an alternative, but direct detection in LTBI and extrapulmonary TB cases is challenging. Mycobacterium tuberculosis grows slowly, has limited hematogenous movement, is protected by a lipid rich cell wall, and produces low levels of secreted factors...
December 2018: Tuberculosis
https://www.readbyqxmd.com/read/30514495/a-new-model-for-chronic-and-reactivation-tuberculosis-infection-with-genetically-attenuated-mycobacterium-tuberculosis-in-mice-with-polar-susceptibility
#5
Tatiana K Kondratieva, Marina A Kapina, Elvira I Rubakova, Elena V Kondratieva, Boris V Nikonenko, Konstantin B Majorov, Alexander V Dyatlov, Irina A Linge, Alexander S Apt
TB infection in mice develops relatively rapidly which interferes with experimental dissection of immune responses and lung pathology features that differ between genetically susceptible and resistant hosts. Earlier we have shown that the M. tuberculosis strain lacking four of five Rpf genes (ΔACDE) is seriously attenuated for growth in vivo. Using this strain, we assessed key parameters of lung pathology, immune and inflammatory responses in chronic and reactivation TB infections in highly susceptible I/St and more resistant B6 mice...
December 2018: Tuberculosis
https://www.readbyqxmd.com/read/30504889/an-explant-technique-for-high-resolution-imaging-and-manipulation-of-mycobacterial-granulomas
#6
Mark R Cronan, Molly A Matty, Allison F Rosenberg, Landry Blanc, Charlie J Pyle, Scott T Espenschied, John F Rawls, Véronique Dartois, David M Tobin
A central and critical structure in tuberculosis, the mycobacterial granuloma consists of highly organized immune cells, including macrophages that drive granuloma formation through a characteristic epithelioid transformation. Difficulties in imaging within intact animals and caveats associated with in vitro assembly models have severely limited the study and experimental manipulation of mature granulomas. Here we describe a new ex vivo culture technique, wherein mature, fully organized zebrafish granulomas are microdissected and maintained in three-dimensional (3D) culture...
December 2018: Nature Methods
https://www.readbyqxmd.com/read/30504725/mycobacterial-infection-is-promoted-by-neutral-sphingomyelinase-2-regulating-a-signaling-cascade-leading-to-activation-of-%C3%AE-1-integrin
#7
Yuqing Wu, Cao Li, Andrea Riehle, Barbara Pollmeier, Erich Gulbins, Heike Grassmé
BACKGROUND/AIMS: Mycobacteria-induced diseases, especially tuberculosis, cause more than 1 million deaths each year, which is higher than any other single bacterial pathogen. Neutral sphingomyelinase 2 (Nsm2) has been implied in many physiological processes and diseases, but the role of Nsm2 in pathogen-host interactions and mycobacterial infections has barely been studied. METHODS: We investigated the role of the Nsm2/ceramide system in systemic infection of mice and murine macrophages with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) as a model for mycobacterial infection...
November 30, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/30500421/mycobacterium-tuberculosis-whib3-maintains-redox-homeostasis-and-survival-in-response-to-reactive-oxygen-and-nitrogen-species
#8
Mansi Mehta, Amit Singh
Mycobacterium tuberculosis (Mtb) survives under oxidatively and nitosatively hostile niches inside host phagocytes. In other bacteria, adaptation to these stresses is dependent upon the redox sensitive two component systems (e.g., ArcAB) and transcription factors (e.g., FNR/SoxR). However, these factors are absent in Mtb. Therefore, it is not completely understood how Mtb maintains survival and redox balance in response to reactive oxygen species (ROS) and reactive nitrogen species (RNS). Here, we present evidences that a 4Fe-4S-cofactor containing redox-sensitive transcription factor (WhiB3) is exploited by Mtb to adapt under ROS and RNS stress...
November 27, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/30487801/the-host-microbiota-contributes-to-early-protection-against-lung-colonization-by-mycobacterium-tuberculosis
#9
Alexia Dumas, Dan Corral, André Colom, Florence Levillain, Antonio Peixoto, Denis Hudrisier, Yannick Poquet, Olivier Neyrolles
Tuberculosis (TB), caused by the airborne bacterial pathogen Mycobacterium tuberculosis , remains a major source of morbidity and mortality worldwide. So far, the study of host-pathogen interactions in TB has mostly focused on the physiology and virulence of the pathogen, as well as, on the various innate and adaptive immune compartments of the host. Microbial organisms endogenous to our body, the so-called microbiota, interact not only with invading pathogens, but also with our immune system. Yet, the impact of the microbiota on host defense against M...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30487797/neutrophils-innate-effectors-of-tb-resistance
#10
REVIEW
Elouise E Kroon, Anna K Coussens, Craig Kinnear, Marianna Orlova, Marlo Möller, Allison Seeger, Robert J Wilkinson, Eileen G Hoal, Erwin Schurr
Certain individuals are able to resist Mycobacterium tuberculosis infection despite persistent and intense exposure. These persons do not exhibit adaptive immune priming as measured by tuberculin skin test (TST) and interferon-γ (IFN-γ) release assay (IGRA) responses, nor do they develop active tuberculosis (TB). Genetic investigation of individuals who are able to resist M. tuberculosis infection shows there are likely a combination of genetic variants that contribute to the phenotype. The contribution of the innate immune system and the exact cells involved in this phenotype remain incompletely elucidated...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30487163/lipg-a-bifunctional-phospholipase-thioesterase-involved-in-mycobacterial-envelope-remodeling
#11
Pierre Santucci, Vanessa Point, Isabelle Poncin, Alexandre Guy, Céline Crauste, Carole Serveau-Avesque, Jean Marie Galano, Christopher D Spilling, Jean François Cavalier, Stéphane Canaan
Tuberculosis caused by Mycobacterium tuberculosis is currently one of the leading causes of death from an infectious agent. The main difficulties encountered in eradicating this bacteria are mainly related to i) a very complex lipid composition of the bacillus cell wall, ii) its ability to hide from the immune system inside the granulomas, and iii) the increasing number of resistant strains. In this context, we were interested in the Rv0646c ( lipGMTB ) gene located upstream to the mmaA cluster which is described as being crucial for the production of cell-wall components and required for the bacilli adaptation and survival in mouse macrophages ...
November 28, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/30484257/newly-synthesized-surfactants-for-surface-mannosylation-of-respirable-sln-assemblies-to-target-macrophages-in-tuberculosis-therapy
#12
Eleonora Maretti, Luca Costantino, Francesca Buttini, Cecilia Rustichelli, Eliana Leo, Eleonora Truzzi, Valentina Iannuccelli
The present study reports about new solid lipid nanoparticle assemblies (SLNas) loaded with rifampicin (RIF) surface-decorated with novel mannose derivatives, designed for anti-tuberculosis (TB) inhaled therapy by dry powder inhaler (DPI). Mannose is considered a relevant ligand to achieve active drug targeting being mannose receptors (MR) overexpressed on membranes of infected alveolar macrophages (AM), which are the preferred site of Mycobacterium tuberculosis. Surface decoration of SLNas was obtained by means of newly synthesized functionalizing compounds used as surfactants in the preparation of carriers...
November 27, 2018: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/30483506/macrophage-exposure-to-polycyclic-aromatic-hydrocarbons-from-wood-smoke-reduces-the-ability-to-control-growth-of-mycobacterium-tuberculosis
#13
Isabel Sada-Ovalle, Leslie Chávez-Galán, Luis Vasquez, Stepahnie Aldriguetti, Irma Rosas-Perez, Alejandra Ramiréz-Venegas, Rogelio Perez-Padilla, Luis Torre-Bouscoulet
Use of solid fuels for cooking or home heating has been related to various diseases of the respiratory tract. Woodsmoke contains a mixture of carcinogenic polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds. Inhalation of these materials induces local and systemic changes in the immune system which may impair critical cell defense mechanisms; however, few studies have investigated the early effects that PAH exposures have on immune cells as macrophages. The aim of this study was to analyze if the pre-exposure to PAHs derived from woodsmoke deteriorates macrophage ability to control the intracellular growth of Mycobacterium tuberculosis ...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/30482832/mycobacterium-tuberculosis-type-vii-secretion-system-effectors-differentially-impact-the-escrt-endomembrane-damage-response
#14
Ekansh Mittal, Michael L Skowyra, Grace Uwase, Emir Tinaztepe, Alka Mehra, Stefan Köster, Phyllis I Hanson, Jennifer A Philips
Intracellular pathogens have varied strategies to breach the endolysosomal barrier so that they can deliver effectors to the host cytosol, access nutrients, replicate in the cytoplasm, and avoid degradation in the lysosome. In the case of Mycobacterium tuberculosis , the bacterium perforates the phagosomal membrane shortly after being taken up by macrophages. Phagosomal damage depends upon the mycobacterial ESX-1 type VII secretion system (T7SS). Sterile insults, such as silica crystals or membranolytic peptides, can also disrupt phagosomal and endolysosomal membranes...
November 27, 2018: MBio
https://www.readbyqxmd.com/read/30478834/expression-and-regulatory-networks-of-mycobacterium-tuberculosis-pe-ppe-family-antigens
#15
REVIEW
Wu Li, Wanyan Deng, Jianping Xie
PE/PPE family antigens are distributed mainly in pathogenic mycobacteria and serve as potential antituberculosis (TB) vaccine components. Some PE/PPE family antigens can regulate the host innate immune response, interfere with macrophage activation and phagolysosome fusion, and serve as major sources of antigenic variation. PE/PPE antigens have been associated with mycobacteria pathogenesis; pe/ppe genes are mainly found in pathogenic mycobacteria and are differentially expressed between Mtb and Mycobacterium bovis...
November 27, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30474709/effect-of-high-glucose-on-human-alveolar-macrophage-phenotype-and-phagocytosis-of-mycobacteria
#16
Jesse Vance, Andres Santos, Laura Sadofsky, Alyn Morice, Jorge Cervantes
PURPOSE: Diabetes mellitus (DBM) reduces immunological activity and increases susceptibility to various infections, including tuberculosis (TB). Human alveolar macrophage (hAM) functions are altered in DBM. METHODS: To mimic hyperglycemic conditions in the lung alveolus, we co-cultured a hAM cell line (Daisy cell line) with human umbilical vein endothelial cells for 48 h in the presence of culture media alone, normal glucose (5 mM), and high glucose (22 mM). Using flow cytometry, immunophenotype characterization included cell surface markers CD 11c, CD14, CD16, CD86, CD163, CD169, CD206, CX3CR-1, CSF-1R, and matrix metalloproteinase-9 (MMP9)...
November 24, 2018: Lung
https://www.readbyqxmd.com/read/30472521/mce-associated-protein-rv0177-alters-the-cell-wall-structure-of-mycobacterium-smegmatis-and-promotes-macrophage-apoptosis-via-regulating-the-cytokines
#17
Shuangquan Yan, Junfeng Zhen, Yue Li, Chenhui Zhang, Andrea Stojkoska, Nzungize Lambert, Qiming Li, Ping Li, Jianping Xie
The success of Mycobacterium tuberculosis as a pathogen largely contributes to its ability to infect, modify and persist within the host cells. M. tuberculosis Rv0177 is a gene of the mce1 operon (Mammalian cell entry), encoding a conserved hypothetical protein, essential for M. tuberculosis survival and up-regulated within murine macrophages. To explore its function, Rv0177 was heterologously expressed in M. smegmatis. The recombinant protein was located in the cell wall. M. smegmatis recombinant strain expressing Rv0177 altered sliding motility, its cell wall architecture and the permeability...
November 22, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/30460206/cite-enzymes-are-essential-for-mycobacterium-tuberculosis-to-establish-infection-in-macrophages-and-guinea-pigs
#18
Garima Arora, Deepika Chaudhary, Saqib Kidwai, Deepak Sharma, Ramandeep Singh
Bacterial citrate lyase activity has been demonstrated in various eukaryotes, bacteria and archaea, underscoring their importance in energy metabolism of the cell. While the bacterial citrate lyase comprises of three different subunits, M. tuberculosis genome lacks CitD and CitF subunits of citrate lyase complex but encodes for 2 homologs of CitE subunits, Rv2498c and Rv3075c. Using temperature sensitive mycobacteriophages, we were able to generate both single and double citE mutant strains of M. tuberculosis ...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/30459752/the-development-of-serum-amyloid-p-as-a-possible-therapeutic
#19
REVIEW
Darrell Pilling, Richard H Gomer
Pentraxins such as serum amyloid P (SAP; also known as PTX2) regulate several aspects of the innate immune system. SAP inhibits the differentiation of monocyte-derived fibroblast-like cells called fibrocytes, promotes the formation of immuno-regulatory macrophages, and inhibits neutrophil adhesion to extracellular matrix proteins. In this minireview, we describe how these effects of SAP have led to its possible use as a therapeutic, and how modulating SAP effects might be used for other therapeutics. Fibrosing diseases such as pulmonary fibrosis, cardiac fibrosis, liver fibrosis, and renal fibrosis are associated with 30-45% of deaths in the US...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30453628/synthesis-and-characterization-of-a-biomimetic-formulation-of-clofazimine-hydrochloride-microcrystals-for-parenteral-administration
#20
Mikhail D Murashov, Jennifer Diaz-Espinosa, Vernon LaLone, Joel W Y Tan, Raluca Laza, Xueding Wang, Kathleen A Stringer, Gus R Rosania
Clofazimine (CFZ) is a broad spectrum antimycobacterial agent recommended by the World Health Organization as a first line treatment for leprosy and second line treatment for multidrug resistant tuberculosis. Oral administration of CFZ leads to a red skin pigmentation side effect. Since CFZ is a weakly basic, red phenazine dye, the skin pigmentation side effect results from lipophilic partitioning of the circulating, free base (neutral) form of CFZ into the skin. Here, we developed a stable and biocompatible formulation of CFZ-HCl microcrystals that mimics the predominant form of the drug that bioaccumulates in macrophages, following long term oral CFZ administration...
November 17, 2018: Pharmaceutics
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