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Mtb with host

Yao-Chung Liu, Chi-Jung Wu, Po-Shen Ko, Sheng-Hsuan Chien, Nai-Wen Fan, Hao-Yuan Wang, Jyh-Pyng Gau, Chia-Jen Liu, Liang-Tsai Hsiao, Tzeon-Jye Chiou, Chun-Yu Liu, Jin-Hwang Liu
BACKGROUND: Mycobacterial infections are important and potentially life-threatening complications after organ transplantations. Notably, for the recipients of allogeneic hematopoietic stem cell transplantation (HSCT), there are a few supporting results to explore post-transplant mycobacterial infections. Taiwan is a high endemic area of the infection. We aim to investigate the incidence, risk factors, and survival of post-transplant mycobacterial infections, including mycobacterium tuberculosis (MTB) and non-tuberculous mycobacterium (NTM)...
July 26, 2018: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
Hawra Al-Ghafli, Sahal Al-Hajoj
BACKGROUND: Despite exerted efforts to control and treat Mycobacterium tuberculosis (MTB) strains, Tuberculosis (TB) remains a public health menace. The emergence of complex drug-resistant profiles, such as multi-drug resistant and extensively drug-resistant MTB strains, emphasizes the need for early diagnosis of resistant cases, shorter treatment options, and effective medical interventions. OBJECTIVE: Solutions for better clinical management of drug resistant cases are either pathogen-centered (novel chemotherapy agents) or host-directed approaches (modulating host immune response to prevent MTB invasion and pathogenesis)...
July 31, 2018: Current Pharmaceutical Biotechnology
Tungadri Bose, Chandrani Das, Anirban Dutta, Vishnuvardhan Mahamkali, Sudipta Sadhu, Sharmila S Mande
BACKGROUND: Mycobacterium tuberculosis infection in humans is often associated with extended period of latency. To adapt to the hostile hypoxic environment inside a macrophage, M. tuberculosis cells undergo several physiological and metabolic changes. Previous studies have mostly focused on inspecting individual facets of this complex process. In order to gain deeper insights into the infection process and to understand the coordination among different regulatory/ metabolic pathways in the pathogen, the current in silico study investigates three aspects, namely, (i) host-pathogen interactions (HPIs) between human and M...
July 27, 2018: BMC Genomics
Supriya Shukla, Edward T Richardson, Michael G Drage, W Henry Boom, Clifford V Harding
Mycobacterium tuberculosis (Mtb) causes persistent infection due to its ability to evade host immune responses. Mtb induces Toll-like receptor 2 (TLR2) signaling, which influences immune responses to Mtb. TLR2 agonists expressed by Mtb include lipoproteins (e.g. LprG), the glycolipid phosphatidylinositol mannoside 6 (PIM6), and the lipoglycan lipomannan (LM). Another Mtb lipoglycan, mannose-capped lipoarabinomannan (ManLAM), lacks TLR2 agonist activity. In contrast, PILAM from M. smegmatis does have TLR2 agonist activity...
July 23, 2018: Infection and Immunity
Juan E López-Ramos, Noe Macías-Segura, Betzaida Cuevas-Cordoba, Zaida Araujo-Garcia, Yadira Bastián, Julio E Castañeda-Delgado, Edgar E Lara-Ramirez, Benjamin Gándara-Jasso, Carmen J Serrano, Eva Salinas, Jose A Enciso-Moreno
BACKGROUND: Pulmonary tuberculosis (PTB) is a public health problem with 10.4 million new cases reported in 2017 (1). According to the World Health Organization (WHO), accurate diagnostic tests based in serum biomarkers to detect new cases of tuberculosis are necessary. AIM OF THE STUDY: To evaluate antibodies against Mycobacterium. tuberculosis (Mtb) peptides (Ab-Mtb) and three soluble host biomarkers by ELISA serial multiple test in sera from non-infected controls (NIC, n = 31), latent tuberculosis (LTB, n = 37) and PTB (n = 28) patients in a diagnosis tuberculosis assay...
July 20, 2018: Archives of Medical Research
Charlotte Genestet, Fanny Bernard-Barret, Elisabeth Hodille, Christophe Ginevra, Florence Ader, Sylvain Goutelle, Gérard Lina, Oana Dumitrescu
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) complex remains a deadly infectious disease worldwide. Mtb is an intracellular pathogen, and autophagy is an essential component of the immune response leading to TB clearance. Anti-TB treatment is based on classical isoniazid (INH) and rifampicin (RIF), but also new drugs, such as linezolid (LNZ) and bedaquiline (BDQ). However, little is known about these antibiotics' impact on Mtb intra-macrophagic behavior independent of their impact on host cells...
July 2018: Tuberculosis
Neetika Jaisinghani, Stanzin Dawa, Kaurab Singh, Ananya Nandy, Dilip Menon, Purva Deepak Bhandari, Garima Khare, Anil Tyagi, Sheetal Gandotra
Pulmonary tuberculosis (TB) exhibits granulomatous inflammation, a site of controlling bacterial dissemination at the cost of host tissue damage. Intrigued by the granuloma type-dependent expression of inflammatory markers in TB, we sought to investigate underlying metabolic changes that drive amplification of inflammation in TB. Here, we show an association of higher inflammation in necrotic granulomas with the presence of triglyceride (TG)-rich foamy macrophages. The conspicuous absence of these macrophages in solid granulomas identified a link between the ensuing pathology and the metabolic programming of foamy macrophages...
2018: Frontiers in Immunology
Priyatam Khadka, Ramesh Bahadur Basnet, Basista Parsad Rijal, Jeevan Bahadur Sherchand
BACKGROUND: Pulmonary nocardiosis is an opportunistic infection in an immunocompromised patient; however, often neglected in the immunocompetent patient from the diagnosis considerations. CASE PRESENTATIONS: We describe a case of pulmonary nocardiosis masquerading renascence of tuberculosis, in a 51-years-Nepali farmer. After a 6 month of presumed successful antitubercular therapy; the patient develops the clinical presentations and radiological features showing similarities with that of tuberculosis and malignancy...
July 17, 2018: BMC Research Notes
David Pajuelo, Norberto Gonzalez-Juarbe, Uday Tak, Jim Sun, Carlos J Orihuela, Michael Niederweis
Mycobacterium tuberculosis (Mtb) kills infected macrophages by inhibiting apoptosis and promoting necrosis. The tuberculosis necrotizing toxin (TNT) is a secreted nicotinamide adenine dinucleotide (NAD+ ) glycohydrolase that induces necrosis in infected macrophages. Here, we show that NAD+ depletion by TNT activates RIPK3 and MLKL, key mediators of necroptosis. Notably, Mtb bypasses the canonical necroptosis pathway since neither TNF-α nor RIPK1 are required for macrophage death. Macrophage necroptosis is associated with depolarized mitochondria and impaired ATP synthesis, known hallmarks of Mtb-induced cell death...
July 10, 2018: Cell Reports
Toidi Adekambi, Chris C Ibegbu, Stephanie Cagle, Susan M Ray, Jyothi Rengarajan
Antigen-specific CD4+ T cell responses to Mycobacterium tuberculosis (Mtb) infection are important for host defense against tuberculosis (TB). However, Mtb-specific IFN-γ-producing T cells do not distinguish active tuberculosis (ATB) patients from individuals with asymptomatic latent Mtb infection (LTBI). We reasoned that the immune phenotype of Mtb-specific IFN-γ+ CD4+ T cells could provide an indirect gauge of Mtb antigen load within individuals. We sought to identify immune markers in Mtb-specific IFN-γ+ CD4+ T cells and hypothesized that expression of caspase-3 Mtb-specific CD4+ T cells would be associated with ATB...
2018: Frontiers in Immunology
Meseret Habtamu, Markos Abebe, Abraham Aseffa, Anne Margarita Dyrhol-Riise, Anne Spurkland, Greger Abrahamsen
There is a lack of suitable correlates of immune protection against Mycobacterium tuberculosis (Mtb) infection. T cells and monocytes play key roles in host immunity against Mtb. Thus, a method that allows assessing their interaction would contribute to the understanding of immune regulation in tuberculosis (TB). We have established imaging flow cytometer (IFC) based in vitro assay for the analysis of early events in T cell-monocyte interaction, upstream of cytokine production and T cell proliferation. This was achieved through short term stimulation of peripheral blood mononuclear cells (PBMC) from healthy Norwegian blood donors with Mycobacterium bovis Bacille Calmette-Guérin (BCG)...
September 2018: Journal of Immunological Methods
Jeroen Maertzdorf, Mario Tönnies, Laura Lozza, Sandra Schommer-Leitner, Hans Mollenkopf, Torsten T Bauer, Stefan H E Kaufmann
Early immune responses to Mycobacterium tuberculosis (Mtb) invasion of the human lung play a decisive role in the outcome of infection, leading to either rapid clearance of the pathogen or stable infection. Despite their critical impact on health and disease, these early host-pathogen interactions at the primary site of infection are still poorly understood. In vitro studies cannot fully reflect the complexity of the lung architecture and its impact on host-pathogen interactions, while animal models have their own limitations...
2018: Frontiers in Immunology
Suyu Mei, Erik K Flemington, Kun Zhang
BACKGROUND: Bacterial invasive infection and host immune response is fundamental to the understanding of pathogen pathogenesis and the discovery of effective therapeutic drugs. However, there are very few experimental studies on the signaling cross-talks between bacteria and human host to date. METHODS: In this work, taking M. tuberculosis H37Rv (MTB) that is co-evolving with its human host as an example, we propose a general computational framework that exploits the known bacterial pathogen protein interaction networks in STRING database to predict pathogen-host protein interactions and their signaling cross-talks...
June 28, 2018: BMC Genomics
Jerome Prusa, Dennis X Zhu, Christina L Stallings
During infection, the host restrains Mycobacterium tuberculosis (Mtb) from proliferating by imposing an arsenal of stresses. Despite this onslaught of attacks, Mtb is able to persist for the lifetime of the host, indicating that this pathogen has substantial molecular mechanisms to resist host-inflicted damage. The stringent response is a conserved global stress response in bacteria that involves the production of the hyperphosphorylated guanine nucleotides ppGpp and pppGpp (collectively called (p)ppGpp). (p)ppGpp then regulates a number of cellular processes to adjust the physiology of the bacteria to promote survival in different environments...
July 1, 2018: Pathogens and Disease
Geanncarlo Lugo-Villarino, Anthony Troegeler, Luciana Balboa, Claire Lastrucci, Carine Duval, Ingrid Mercier, Alan Bénard, Florence Capilla, Talal Al Saati, Renaud Poincloux, Ivanela Kondova, Frank A W Verreck, Céline Cougoule, Isabelle Maridonneau-Parini, Maria Del Carmen Sasiain, Olivier Neyrolles
DC-SIGN (CD209/CLEC4L) is a C-type lectin receptor (CLR) that serves as a reliable cell-surface marker of interleukin 4 (IL-4)-activated human macrophages [M(IL-4)], which historically represent the most studied subset within the M2 spectrum of macrophage activation. Although DC-SIGN plays important roles in Mycobacterium tuberculosis (Mtb) interactions with dendritic cells, its contribution to the Mtb-macrophage interaction remains poorly understood. Since high levels of IL-4 are correlated with tuberculosis (TB) susceptibility and progression, we investigated the role of DC-SIGN in M(IL-4) macrophages in the TB context...
2018: Frontiers in Immunology
Laura E Gleeson, Daniel Ryan, Seonadh M O'Leary, Anne Marie McLaughlin, Frederick J Sheedy, Joseph M Keane
RATIONALE: Smoking is a major risk factor driving the tuberculosis (TB) epidemic and smokers' alveolar macrophages (AM) demonstrate significant immune defects following infection. Recently, macrophage glycolytic reprogramming has emerged as crucial in the early host immune response to Mycobacterium tuberculosis (Mtb) infection. OBJECTIVES: To compare baseline metabolic characteristics and the glycolytic response to infection of human AM from smokers and non-smokers...
June 26, 2018: American Journal of Respiratory Cell and Molecular Biology
Amber C Bonds, Nicole S Sampson
Mycobacterium tuberculosis (Mtb) is the epitome of persistent. Mtb is the pathogen that causes tuberculosis, the leading cause of death by infection worldwide. The success of this pathogen is due in part to its clever ability to adapt to its host environment and its effective manipulation of the host immune system. A major contributing factor to the survival and virulence of Mtb is its acquisition and metabolism of host derived lipids including cholesterol. Accumulating evidence suggests that the catabolism of cholesterol during infection is highly regulated by cholesterol catabolites...
June 12, 2018: Current Opinion in Chemical Biology
Richard M Johnson, Kathleen A McDonough
Mycobacterium tuberculosis (Mtb) is one of the most successful microbial pathogens, and currently infects over a quarter of the world's population. Mtb's success depends on the ability of the bacterium to sense and respond to dynamic and hostile environments within the host, including the ability to regulate bacterial metabolism and interactions with the host immune system. One of the ways Mtb senses and responds to conditions it faces during infection is through the concerted action of multiple cyclic nucleotide signaling pathways...
July 1, 2018: Pathogens and Disease
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
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
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