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macrophage tuberculosis

Helen A Fletcher, Mitali Chatterjee, Andrea Cooper, Tracy Hussell, Paul M Kaye, Joann Prior, Rajko Reljic, Samantha Vermaak, Martin Vordermeier, Ann Williams, Helen McShane
For several complex intracellular pathogens, we have an urgent need for effective vaccines and yet there are common barriers to vaccine development. These diseases, including tuberculosis, leishmaniasis, leprosy and melioidosis, cause a huge burden of disease and disproportionately affect low and middle income countries. They are therefore often neglected due to the marginalisation of affected populations and the poor predicted commercial return on investment. Barriers to vaccine development include an incomplete understanding of protective immunity and translation from the bench into clinical vaccine trials...
2018: F1000Research
Preeti Jain, Basanti Malakar, Mehak Zahoor Khan, Savita Lochab, Archana Singh, Vinay K Nandicoori
Identifying and characterizing the individual contributors to bacterial cellular elongation and division will improve our understanding of their impact on cell growth and division. Here, we delineated the role of ftsQ, a terminal gene of the highly conserved division cell wall (dcw) operon, in growth, survival, and cell length maintenance in the human pathogen Mycobacterium tuberculosis (Mtb). We found that FtsQ overexpression significantly increases the cell length and number of multiseptate cells. FtsQ depletion in Mtb resulted in cells that were shorter than WT cells during the initial growth stages (4 days after FtsQ depletion), but were longer than WT cells at later stages (10 days after FtsQ depletion), and compromised the survival in vitro and in differentiated THP1 macrophages...
June 14, 2018: Journal of Biological Chemistry
Jongmin Sim, Hyun Hee Koh, Sangjoon Choi, Jinah Chu, Tae Sung Kim, Hojoong Kim, Joungho Han
Background: Pulmonary nodular lymphoid hyperplasia (PNLH) is a non-neoplastic pulmonary lymphoid disorder that can be mistaken for malignancy on radiography. Herein, we present nine cases of PNLH, emphasizing clinicoradiological findings and histological features. Materials and Methods: We analyzed radiological and clinicopathological features from the electronic medical records of nine patients (eight females and one male) diagnosed with PNLH. IgG and IgG4 immunohistochemical staining was performed in three patients...
June 15, 2018: Journal of Pathology and Translational Medicine
Jason D Simmons, Catherine M Stein, Chetan Seshadri, Monica Campo, Galit Alter, Sarah Fortune, Erwin Schurr, Robert S Wallis, Gavin Churchyard, Harriet Mayanja-Kizza, W Henry Boom, Thomas R Hawn
Mycobacterium tuberculosis is a leading cause of mortality worldwide and establishes a long-lived latent infection in a substantial proportion of the human population. Multiple lines of evidence suggest that some individuals are resistant to latent M. tuberculosis infection despite long-term and intense exposure, and we term these individuals 'resisters'. In this Review, we discuss the epidemiological and genetic data that support the existence of resisters and propose criteria to optimally define and characterize the resister phenotype...
June 12, 2018: Nature Reviews. Immunology
Michael D Stutz, Samar Ojaimi, Gregor Ebert, Marc Pellegrini
The dwindling list of antimicrobial agents exhibiting broad efficacy against clinical strains of Mycobacterium tuberculosis (Mtb) has forced the medical community to redefine current approaches to the treatment of tuberculosis (TB). Host receptor-interacting protein kinase 3 (RIPK3) has been flagged recently as a potential target, given that it is believed to regulate necroptosis-independent signaling pathways, which have been implicated in exacerbating several inflammatory conditions and which reportedly play a role in the necrosis of Mtb-infected macrophages...
2018: Frontiers in Immunology
Lingbo Fan, Xiaoyu Wu, Chunyan Jin, Fengge Li, Sidong Xiong, Yuanshu Dong
Tuberculosis is a severe contagious disease caused by Mycobacterium tuberculosis (Mtb). To develop new vaccines and medicine against TB, there is an urgent need to provide insights into the mechanisms by which Mtb induces tuberculosis. In this study, we found that secreted Mtb virulence factor MptpB significantly enhanced the survival of H37Rv in macrophages. MptpB suppressed the production of iNOS, the expression of inflammatory factors IL-1β and IL-6, as well as the apoptosis of the macrophage in Mtb infected RAW264...
2018: Frontiers in Cellular and Infection Microbiology
Gerald C Smaldone
Pulmonary diseases frequently involve imbalances in immunity. The inability to control bacteria in tuberculosis is a failed response to a pathogen. Idiopathic pulmonary fibrosis (IPF), a progressive fibrotic lung disease, can lead to respiratory failure and death within 3 years of diagnosis. Chronic obstructive pulmonary disease (COPD) progresses until death and in recent years has been labeled an autoimmune disease. Proposed mechanistic pathways of pathophysiology involve uncontrolled healing governed by pro-fibrotic cytokines that are unresponsive to the standard anti-inflammatory agents (e...
June 7, 2018: Advanced Drug Delivery Reviews
Mahendravarman Mohanraj, Ponarulselvam Sekar, Horng-Huei Liou, Shwu-Fen Chang, Wan-Wan Lin
Microglial activation has long been recognized as a hallmark of neuroinflammation. Recently, the bacillus Calmette-Guerin (BCG) vaccine has been reported to exert neuroprotective effects against several neurodegenerative disorders. Trehalose-6,6'-dibehenate (TDB) is a synthetic analogue of trehalose-6,6'-dimycolate (TDM, also known as the mycobacterial cord factor) and is a new adjuvant of tuberculosis subunit vaccine currently in clinical trials. Both TDM and TDB can activate macrophages and dendritic cells through binding to C-type lectin receptor Mincle; however, its action mechanism in microglia and their relationship with neuroinflammation are still unknown...
June 6, 2018: Molecular Neurobiology
Mohlopheni J Marakalala, Fernando O Martinez, Annette Plüddemann, Siamon Gordon
Macrophages play a central role in tuberculosis, as the site of primary infection, inducers and effectors of inflammation, innate and adaptive immunity, as well as mediators of tissue destruction and repair. Early descriptions by pathologists have emphasized their morphological heterogeneity in granulomas, followed by delineation of T lymphocyte-dependent activation of anti-mycobacterial resistance. More recently, powerful genetic and molecular tools have become available to describe macrophage cellular properties and their role in host-pathogen interactions...
2018: Frontiers in Microbiology
Sulayman Benmerzoug, Fabio Vitarelli Marinho, Stéphanie Rose, Claire Mackowiak, David Gosset, Delphine Sedda, Emeline Poisson, Catherine Uyttenhove, Jacques Van Snick, Muazzam Jacobs, Irene Garcia, Bernhard Ryffel, Valerie F J Quesniaux
Host directed immunomodulation represents potential new adjuvant therapies in infectious diseases such as tuberculosis. Major cytokines like TNFα exert a multifold role in host control of mycobacterial infections. GM-CSF and its receptor are over-expressed during acute M. tuberculosis infection and we asked how GM-CSF neutralization might affect host response, both in immunocompetent and in immunocompromised TNFα-deficient mice. GM-CSF neutralizing antibodies, at a dose effectively preventing acute lung inflammation, did not affect M...
June 5, 2018: Scientific Reports
Elias R Gerrick, Thibault Barbier, Michael R Chase, Raylin Xu, Josie François, Vincent H Lin, Matthew J Szucs, Jeremy M Rock, Rushdy Ahmad, Brian Tjaden, Jonathan Livny, Sarah M Fortune
One key to the success of Mycobacterium tuberculosis as a pathogen is its ability to reside in the hostile environment of the human macrophage. Bacteria adapt to stress through a variety of mechanisms, including the use of small regulatory RNAs (sRNAs), which posttranscriptionally regulate bacterial gene expression. However, very little is currently known about mycobacterial sRNA-mediated riboregulation. To date, mycobacterial sRNA discovery has been performed primarily in log-phase growth, and no direct interaction between any mycobacterial sRNA and its targets has been validated...
June 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jennifer A Juno, Jillian L M Waruk, Kathleen M Wragg, Christine Mesa, Carmen Lopez, Joe Bueti, Stephen J Kent, T Blake Ball, Sandra A Kiazyk
Background: End-stage renal disease (ESRD) is associated with an increased susceptibility to infectious diseases, including infection with Mycobacterium tuberculosis (Mtb) . Mucosal-associated invariant T (MAIT) cells recognize vitamin B metabolites produced by many bacterial species, including Mtb, and may play an important role in providing protective immunity against tuberculosis infection in the lung. To date, little is known about MAIT cell frequency, phenotype, or function in ESRD patients...
2018: Frontiers in Immunology
Maha Ahmed Al-Mozaini, Anthony G Tsolaki, Munirah Abdul-Aziz, Suhair M Abozaid, Mohammed N Al-Ahdal, Ansar A Pathan, Valarmathy Murugaiah, Evgeny M Makarov, Anuvinder Kaur, Robert B Sim, Uday Kishore, Lubna Kouser
Mycobacterium tuberculosis can proficiently enter macrophages and diminish complement activation on its cell surface. Within macrophages, the mycobacterium can suppress macrophage apoptosis and survive within the intracellular environment. Previously, we have shown that complement regulatory proteins such as factor H may interfere with pathogen-macrophage interactions during tuberculosis infection. In this study, we show that Mycobacterium bovis BCG binds properdin, an upregulator of the complement alternative pathway...
2018: Frontiers in Immunology
Michelle M Coleman, Sharee A Basdeo, Amy M Coleman, Clíona Ní Cheallaigh, Celia Peral de Castro, Anne Marie McLaughlin, Padraic J Dunne, James Harris, Joseph Keane
Vitamin A deficiency strongly predicts the risk of developing tuberculosis (TB) in individuals exposed to Mycobacterium tuberculosis (Mtb). The burden of antibiotic resistant TB is increasing globally therefore there is an urgent need to develop host-directed adjunctive therapies to treat TB. Alveolar macrophages (AM), the niche cell for Mtb, metabolize vitamin A to all-trans retinoic acid (atRA), which influences host immune responses. We sought to determine the mechanistic effects of atRA on the host immune response to intracellular bacterial infection in primary human and murine macrophages...
May 31, 2018: American Journal of Respiratory Cell and Molecular Biology
Li Li, Yong Cheng, Scott Emrich, Jeffrey Schorey
Endothelial cells play an essential role in regulating an immune response through promoting leukocyte adhesion and cell migration and production of cytokines such as TNFα. Regulation of endothelial cell immune function is tightly regulated and recent studies suggest that extracellular vesicles (EVs) are prominently involved in this process. However, the importance of EVs in regulating endothelial activation in the context of a bacterial infection is poorly understood. To begin addressing this knowledge gap we characterized the endothelial cell response to EVs released from Mycobacterium tuberculosis (Mtb) infected macrophages...
2018: PloS One
Fang-Yi Su, Jasmin Chen, Hye-Nam Son, Abby M Kelly, Anthony J Convertine, T Eoin West, Shawn J Skerrett, Daniel M Ratner, Patrick S Stayton
Pulmonary intracellular infections, such as tuberculosis, anthrax, and tularemia, have remained a significant challenge to conventional antibiotic therapy. Ineffective antibiotic treatment of these infections can lead not only to undesired side effects, but also to the emergence of antibiotic resistance. Aminoglycosides (e.g., streptomycin) have long been part of the therapeutic regiment for many pulmonary intracellular infections. Their bioavailability for intracellular bacterial pools, however, is limited by poor membrane permeability and rapid elimination...
May 31, 2018: Biomaterials Science
Guillermina J Baay-Guzman, Marco A Duran-Padilla, Jesus Rangel-Santiago, Belen Tirado-Rodriguez, Gabriela Antonio-Andres, Jorge Barrios-Payan, Dulce Mata-Espinosa, Miguel Klunder-Klunder, Mario I Vega, Rogelio Hernandez-Pando, Sara Huerta-Yepez
AIM: Investigate the role of hypoxia-inducible factor-1α (HIF-1α) in pulmonary tuberculosis (TB). METHODS & RESULTS: A model of progressive pulmonary TB in BALB/c mice, immunohistochemistry and digital pathology were used. High HIF-1α expression was observed during early TB in activated macrophages. During late TB, even higher HIF-1α expression was observed in foamy macrophages, which are resistant to apoptosis. Blocking HIF-1α during early infection with 2-methoxyestradiol worsened the disease, while during late TB, it induced macrophage apoptosis and decreased bacillary loads...
May 31, 2018: Future Microbiology
Audrey C Papp, Abul K Azad, Maciej Pietrzak, Amanda Williams, Samuel K Handelman, Robert P Igo, Catherine M Stein, Katherine Hartmann, Larry S Schlesinger, Wolfgang Sadee
Human alveolar macrophages (HAM) are primary bacterial niche and immune response cells during Mycobacterium tuberculosis (M.tb) infection, and human blood monocyte-derived macrophages (MDM) are a model for investigating M.tb-macrophage interactions. Here, we use a targeted RNA-Seq method to measure transcriptome-wide changes in RNA expression patterns of freshly obtained HAM (used within 6 h) and 6 day cultured MDM upon M.tb infection over time (2, 24 and 72 h), in both uninfected and infected cells from three donors each...
2018: PloS One
Ankur Bothra, Prabhakar Arumugam, Vipul Panchal, Dilip Menon, Sonali Srivastava, Deepthi Shankaran, Ananya Nandy, Neetika Jaisinghani, Archana Singh, Rajesh S Gokhale, Sheetal Gandotra, Vivek Rao
The mycobacterial cell wall is a chemically complex array of molecular entities that dictate the pathogenesis of Mycobacterium tuberculosis. Biosynthesis and maintenance of this dynamic entity in mycobacterial physiology is still poorly understood. Here we demonstrate a requirement for M. tuberculosis MmpL11 in the maintenance of the cell wall architecture and stability in response to surface stress. In the presence of a detergent like Tyloxapol, a mmpL11 deletion mutant suffered from a severe growth attenuation as a result of altered membrane polarity, permeability and severe architectural damages...
May 29, 2018: Scientific Reports
Jia-Yih Feng, Wei-Juin Su, Sheng-Wei Pan, Yi-Chen Yeh, Yung-Yang Lin, Nien-Jung Chen
Triggering receptor expressed on myeloid cells 1 (TREM-1) amplifies inflammatory responses and is upregulated during sepsis and pulmonary infection. The association between serum soluble TREM-1 (sTREM-1) level and pulmonary tuberculosis (PTB) disease deserves investigation. In the present study, patients with PTB, latent TB infection (LTBI), and non-TB, non-LTBI subjects were prospectively enrolled and serum levels of sTREM-1, sTREM-2, and C-reactive protein (CRP) were measured. We correlated serum biomarkers and clinical presentations and treatment outcomes of PTB cases...
May 29, 2018: Scientific Reports
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