Read by QxMD icon Read

Pathogenesis AND Tuberculosis

Swati Jaiswal, Kishore K Srivastava
Mycobacterium tuberculosis (MTB) is a successful pathogen which increases persistence inside the host macrophage by subverting its defence mechanism. Mycobacteria regulate the pathogenesis and intracellular survival by controlling its interaction with host protein(s). Galectin 3 is a member of the β-galactoside binding gene family which is involved in several biological functions. In the present study we have expressed the mycobacterial protein tyrosine kinase (PtkA) in the cytosol of host macrophages through a eukaryotic promoter vector and found that it down-regulates Galectin 3...
March 12, 2018: Biochemical and Biophysical Research Communications
Yu Wang, Miao-Miao Zhang, Wei-Wei Huang, Shou-Quan Wu, Ming-Gui Wang, Xiao-Yan Tang, Andrew J Sandford, Jian-Qing He
Background: The toll-like receptor 2 (TLR2)-mediated immune response is critical for host defense against Mycobacterium tuberculosis . There is evidence that TLR10, a TLR2 signaling modulator, may be involved in progression of tuberculosis (TB). Methods: Using a self-validating case-control design, we tested for an association between seven TLR10 polymorphisms and susceptibility to TB in three independent series with two distinct populations. Single-nucleotide polymorphism (SNP) genotypes were determined by the SNPscanTM method...
2018: Frontiers in Immunology
Chong Wang, Su Yang, Chang-Ming Liu, Ting-Ting Jiang, Zhong-Liang Chen, Hui-Hui Tu, Lian-Gen Mao, Zhong-Jie Li, Ji-Cheng Li
Rapid and efficient methods for the determination of cured pulmonary tuberculosis (TB) are lacking. We screened serum miRNAs using the Solexa sequencing method among untreated TB patients, two-month treated TB patients, cured TB patients, and healthy controls. A total of 100 differentially expressed miRNAs were identified in cured TB patients, including 37 up-regulated (fold change >1.50, P < 0.05) and 63 down-regulated (fold change <0.60, P < 0.05) miRNAs. Gene ontology (GO) enrichment analysis revealed that most of the predicted genes were present in the nucleus with a strong protein binding function...
January 2018: Tuberculosis
Mathieu Garand, Martin Goodier, Olumuyiwa Owolabi, Simon Donkor, Beate Kampmann, Jayne S Sutherland
Tuberculosis (TB) is still a global health concern, especially in resource-poor countries such as The Gambia. Defining protective immunity to TB is challenging: its pathogenesis is complex and involves several cellular components of the immune system. Recent works in vaccine development suggest important roles of the innate immunity in natural protection to TB, including natural killer (NK) cells. NK cells mediate cellular cytotoxicity and cytokine signaling in response to Mycobacterium tuberculosis (Mtb). NK cells can display specific memory-type markers to previous antigen exposure; thus, bridging innate and adaptive immunity...
2018: Frontiers in Immunology
Shahrad Hakimian, Yevgeniy Popov, Abbas H Rupawala, Karen Salomon-Escoto, Steven Hatch, Randall Pellish
Background: Tumor necrosis factor alpha (TNFα) is a key cytokine in both the pathogenesis of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) and the host defense against tuberculosis (TB). Consequently, anti-TNFα medications result in an increased risk of latent TB infection (LTBI) reactivation. Here, we sought to evaluate the factors affecting the results of QuantiFERON-TB Gold In-Tube (QFT-GIT) assay as a screening tool for LTBI. Methods: We conducted an observational, retrospective study in patients with IBD and RA who underwent LTBI screening using QFT-GIT at UMass Memorial Medical Center between 2008 and 2016 prior to initiation of anti-TNF medications...
2018: Biologics: Targets & Therapy
Tilman E Klassert, Surabhi Goyal, Magdalena Stock, Dominik Driesch, Abid Hussain, Luis Carlos Berrocal-Almanza, Rajashekar Myakala, Gaddam Sumanlatha, Vijayalakshmi Valluri, Niyaz Ahmed, Ralf R Schumann, Carlos Flores, Hortense Slevogt
Tuberculosis (TB) is a multifactorial disease governed by bacterial, host and environmental factors. On the host side, growing evidence shows the crucial role that genetic variants play in the susceptibility to Mycobacterium tuberculosis (Mtb) infection. Such polymorphisms have been described in genes encoding for different cytokines and pattern recognition receptors (PRR), including numerous Toll-like receptors (TLRs). In recent years, several members of the C-type lectin receptors (CTLRs) have been identified as key PRRs in TB pathogenesis...
2018: Frontiers in Immunology
Valentin Trofimov, Sébastien Kicka, Sabrina Mucaria, Nabil Hanna, Fernando Ramon-Olayo, Laura Vela-Gonzalez Del Peral, Joël Lelièvre, Lluís Ballell, Leonardo Scapozza, Gurdyal S Besra, Jonathan A G Cox, Thierry Soldati
Tuberculosis remains a serious threat to human health world-wide, and improved efficiency of medical treatment requires a better understanding of the pathogenesis and the discovery of new drugs. In the present study, we performed a whole-cell based screen in order to complete the characterization of 168 compounds from the GlaxoSmithKline TB-set. We have established and utilized novel previously unexplored host-model systems to characterize the GSK compounds, i.e. the amoeboid organisms D. discoideum and A. castellanii, as well as a microglial phagocytic cell line, BV2...
March 2, 2018: Scientific Reports
Shruthi Ravimohan, Hardy Kornfeld, Drew Weissman, Gregory P Bisson
A past history of pulmonary tuberculosis (TB) is a risk factor for long-term respiratory impairment. Post-TB lung dysfunction often goes unrecognised, despite its relatively high prevalence and its association with reduced quality of life. Importantly, specific host and pathogen factors causing lung impairment remain unclear. Host immune responses probably play a dominant role in lung damage, as excessive inflammation and elevated expression of lung matrix-degrading proteases are common during TB. Variability in host genes that modulate these immune responses may determine the severity of lung impairment, but this hypothesis remains largely untested...
March 31, 2018: European Respiratory Review: An Official Journal of the European Respiratory Society
Hanif Esmail, Catherine Riou, Elsa du Bruyn, Rachel Pei-Jen Lai, Yolande X R Harley, Graeme Meintjes, Katalin A Wilkinson, Robert J Wilkinson
Globally, about 36.7 million people were living with HIV infection at the end of 2015. The most frequent infection co-occurring with HIV-1 is Mycobacterium tuberculosis-389,000 deaths per annum are attributable to HIV tuberculosis, 75% of those occurring in Africa. HIV-1 infection increases the risk of tuberculosis by a factor of up to 26 and alters its clinical presentation, complicates diagnosis and treatment, and worsens outcome. Although HIV-1-induced depletion of CD4+ T cells underlies all these effects, more widespread immune deficits also contribute to susceptibility and pathogenesis...
February 28, 2018: Annual Review of Immunology
Violette Dirix, Véronique Corbière, Chloé Wyndham-Thomas, Elodie Selis, Sabine Allard, Maya Hites, Laetitia Aerts, Thomas Giese, Françoise Mascart
BACKGROUND: The immune mechanisms underlying the pathogenesis of tuberculosis (TB) need better understanding to improve TB management, as the disease still causes more than 1.5 million deaths annually. This study tested the hypothesis that a modulation of the proportions or activation status of APC during Mycobacterium tuberculosis infection may impact on the course of the disease. PROCEDURE: Proportions of circulating APC subsets and the expression of stimulatory (CD86), inhibitory (ILT-3, ILT-4, ILT-7), or apoptosis-inducing (PDL-1, PDL-2) molecules were analyzed in 2 independent cohorts, on blood monocytes and dendritic cell (DC) subsets from patients with active or latent TB infection (aTB /LTBI) and from uninfected subjects...
February 28, 2018: Journal of Leukocyte Biology
Muthupandian Saravanan, Selam Niguse, Mahmud Abdulkader, Ephrem Tsegay, Haftamu Hailekiros, Atsbeha Gebrekidan, Tadele Araya, Arivalagan Pugazhendhi
Tuberculosis (TB) remains a major global health problem and ranks as the second leading cause of death among deaths caused by infectious diseases worldwide. Although the availability of short-course regimens as first-line anti-tuberculosis drugs, the emergence of drug-resistant Mycobacterium tuberculosis strains pose a major challenge to the prevention and control efforts of national tuberculosis programs (NTPs). M. tuberculosis changes its cellular environment with the mechanisms that have been evolved since prehistoric times...
February 24, 2018: Microbial Pathogenesis
Pratap C Mali, Laxman S Meena
The ability of Mycobacterium tuberculosis (M. tuberculosis) to accumulate lipid-rich molecules as an energy source obtained from host cell debris remains interesting. Additionally, the potential of M. tuberculosis to survive under different stress conditions leading to its dormant state in pathogenesis remains elusive. The exact mechanism by which these lipid bodies generated in M. tuberculosis infection and utilized by bacilli inside infected macrophage for its survival is still not understood. In this, during bacillary infection, many metabolic pathways are involved that influence the survival of M...
March 2018: Journal of Biosciences
Tiffany A Claeys, Richard T Robinson
Nontuberculous mycobacteria (NTM) include species that colonize human epithelia, as well as species that are ubiquitous in soil and aquatic environments. NTM that primarily inhabit soil and aquatic environments include the Mycobacterium avium complex (MAC, M. avium and Mycobacterium intracellulare ) and the Mycobacterium abscessus complex (MABSC, M. abscessus subspecies abscessus , massiliense , and bolletii ), and can be free-living, biofilm-associated, or amoeba-associated. Although NTM are rarely pathogenic in immunocompetent individuals, those who are immunocompromised - due to either an inherited or acquired immunodeficiency - are highly susceptible to NTM infection (NTMI)...
February 26, 2018: Journal of Bacteriology
Archita Mishra, Ashalatha S Mamidi, Raju S Rajmani, Ananya Ray, Rajanya Roy, Avadhesha Surolia
The existing treatment regime against tuberculosis is not adequate, and novel therapeutic interventions are required to target Mycobacterium tuberculosis (Mtb) pathogenesis. We report Pranlukast (PRK) as a novel allosteric inhibitor of Mtb 's arginine biosynthetic enzyme, Ornithine acetyltransferase ( Mt ArgJ). PRK treatment remarkably abates the survival of free as well as macrophage-internalized Mtb , and shows enhanced efficacy in combination with standard-of-care drugs. Notably, PRK also reduces the 5-lipoxygenase (5-LO) signaling in the infected macrophages, thereby surmounting an enhanced response against intracellular pathogen...
February 26, 2018: EMBO Molecular Medicine
Danping Hong, Jiongyan Ding, Ouyang Li, Quan He, Minxia Ke, Mengyi Zhu, Lili Liu, Wen-Bin Ou, Yulong He, Yuehong Wu
BACKGROUND: Induced pluripotent stem cells (iPS) represent an innovative source for the standardized in vitro generation of macrophages (Mφ). Mφ show great promise in disease pathogenesis, particularly tuberculosis. However, there is no information about human iPS-derived (hiPS) macrophages (hiPS-Mφ) in response to tuberculosis infection. METHODS: In the present study, macrophages derived from hiPS were established via embryoid body (EB) formation by using feeder-free culture conditions, and the human monocyte cell line THP-1 (THP-1-Mφ) was used as control...
February 26, 2018: Stem Cell Research & Therapy
Ana Negri, Prisca Javidnia, Ran Mu, Xiaojie Zhang, Jeremie Vendome, Ben Gold, Julia Roberts, Dipti Barman, Thomas Ioerger, James C Sacchettini, Xiuju Jiang, Kristin Burns-Huang, Thulasi Warrier, Yan Ling, J David Warren, Deena A Oren, Thijs Beuming, Hongyao Wang, Jie Wu, Haitao Li, Kyu Y Rhee, Carl F Nathan, Gang Liu, Selin Somersan-Karakaya
The success of Mycobacterium tuberculosis (Mtb) as a pathogen depends on the redundant and complex mechanisms it has evolved for resisting nitrosative and oxidative stresses inflicted by host immunity. Improving our understanding of these defense pathways can reveal vulnerable points in Mtb pathogenesis. In this study, we combined genetic, structural, computational, biochemical, and biophysical approaches to identify a novel enzyme class represented by Rv2466c. We show that Rv2466c is a mycothiol-dependent nitroreductase of Mtb and can reduce the nitro group of a novel mycobactericidal compound using mycothiol as a cofactor...
February 21, 2018: ACS Infectious Diseases
Rui Yang, Enzhuo Yang, Ling Shen, Robert L Modlin, Hongbo Shen, Zheng W Chen
The ability of Mycobacterium tuberculosis to block host antimicrobial responses in infected cells provides a key mechanism for disease pathogenesis. The immune system has evolved to overcome this blockade to restrict the infection, but it is not clear whether two key innate cytokines (IL-12/IL-18) involved in host defense can enhance antimycobacterial mechanisms. In this study, we demonstrated that the combination of IL-12 and IL-18 triggered an antimicrobial response against mycobacteria in infected macrophages (THP-1 and human primary monocyte-derived macrophages) and pulmonary epithelial A549 cells...
February 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Gina Leisching, Ian Wiid, Bienyameen Baker
Evidence to-date collectively points to a detrimental role of the type I IFN response during tuberculosis. The mechanisms underpinning the IFNαβ-mediated exacerbation of the disease is unclear. The 2'-5'-oligoadenylate synthetases (OAS), namely OAS1, OAS2 and OAS3 are part of the interferon-induced genes which until now have been synonymous with an anti-viral function. Blood transcriptome profiling has continuously observed their upregulation in a number of gene expression signatures which discriminate active TB from latent TB infection, however the role of the OASs and the effect that their expression has on the pathogenesis and persistence of TB is unknown...
February 14, 2018: Journal of Infectious Diseases
Pooja Singh, Selvakumar Subbian
Tuberculosis (TB) remains as one of the leading killer infectious diseases of humans. At present, the standard therapeutic regimen to treat TB comprised of multiple antibiotics administered for a minimum of six months. Although these drugs are useful in controlling TB burden globally, they have not eliminated the disease. In addition, the lengthy duration of treatment with multiple drugs contributes to patient non-compliance that can result in the development of drug resistant strains (MDR and XDR) of Mycobacterium tuberculosis (Mtb), the causative agent of TB...
2018: Frontiers in Microbiology
Gustavo Guimarães Moreira Balbi, Francinne Machado-Ribeiro, Cláudia D L Marques, Flávio Signorelli, Roger Abramino Levy
PURPOSE OF REVIEW: Tuberculosis (TB) is a millenarian chronic infection and, yet, remains a major global health problem. The interaction between systemic lupus erythematosus (SLE) and TB is complex, as one seems to be a risk factor for the development of the other. SLE patients are more likely to develop TB, that is more frequently extrapulmonary, with more extensive pulmonary involvement, and with a higher relapse rate. RECENT FINDINGS: Different studies suggest that TB is more prevalent in SLE patients and that TB may actually be a risk factor for the development of the disease...
February 12, 2018: Current Opinion in Rheumatology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"