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M.tuberculosis immune

Yuko Hamaguchi, Takayuki Yamaguchi, Hiroshi Nishiura
To assess tuberculosis transmission frequency at a population level, the age-dependent Mantoux test has been used widely to estimate the annual risk of infection (ARI) with Mycobacterium tuberculosis. However, the widespread Bacille Calmette-Guerin (BCG) immunization program implemented in Japan in the 20th century has made natural infections with M. tuberculosis difficult to distinguish from immune responses against this vaccine. Consequently, a recognized alternative method for measuring the frequency of primary infections, the interferon-gamma release assay (IGRA), which partially decays as a function of time after infection, is used...
October 10, 2018: Journal of Theoretical Biology
Flavia Squeglia, Alessia Ruggiero, Rita Berisio
The scenario of chemical reactions prompted by the infection by Mycobacterium tuberculosis is huge. The infection generates a localized inflammatory response, with the recruitment of neutrophils, monocytes, and T-lymphocytes. Consequences of this immune reaction can be the eradication or containment of the infection, but these events can be deleterious to the host inasmuch as lung tissue can be destroyed. Indeed, a hallmark of tuberculosis (TB) is the formation of lung cavities, which increase disease development and transmission, as they are sites of high mycobacterial burden...
October 11, 2018: Biochemical Journal
Anthony M Cadena, Forrest F Hopkins, Pauline Maiello, Allison F Carey, Eileen A Wong, Constance J Martin, Hannah P Gideon, Robert M DiFazio, Peter Andersen, Philana Ling Lin, Sarah M Fortune, JoAnne L Flynn
For many pathogens, including most targets of effective vaccines, infection elicits an immune response that confers significant protection against reinfection. There has been significant debate as to whether natural Mycobacterium tuberculosis (Mtb) infection confers protection against reinfection. Here we experimentally assessed the protection conferred by concurrent Mtb infection in macaques, a robust experimental model of human tuberculosis (TB), using a combination of serial imaging and Mtb challenge strains differentiated by DNA identifiers...
October 12, 2018: PLoS Pathogens
Somdeb BoseDasgupta, Jean Pieters
Macrophages, being the cornerstone of the immune system, have adapted the ancient nutrient acquisition mechanism of phagocytosis to engulf various infectious organisms thereby helping to orchestrate an appropriate host response. Phagocytosis refers to the process of internalization and degradation of particulate material, damaged and senescent cells and microorganisms by specialized cells, after which the vesicle containing the ingested particle, the phagosome, matures into acidic phagolysosomes upon fusion with hydrolytic enzyme-containing lysosomes...
October 10, 2018: Seminars in Immunopathology
Anthony M Cadena, Yixuan Ma, Tao Ding, MacKenzie Bryant, Pauline Maiello, Adam Geber, Philana Ling Lin, JoAnne L Flynn, Elodie Ghedin
BACKGROUND: The specific interactions of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), and the lung microbiota in infection are entirely unexplored. Studies in cancer and other infectious diseases suggest that there are important exchanges occurring between host and microbiota that influence the immunological landscape. This can result in alterations in immune regulation and inflammation both locally and systemically. To assess whether Mtb infection modifies the lung microbiome, and identify changes in microbial abundance and diversity as a function of pulmonary inflammation, we compared infected and uninfected lung lobe washes collected serially from 26 macaques by bronchoalveolar lavage over the course of infection...
October 9, 2018: Microbiome
F Teixeira-Lopes, S Alfarroba, A Dinis, M C Gomes, A Tavares
INTRODUCTION: Ocular tuberculosis (OTB) is a rare form of tuberculosis. Diagnosis is usually presumptive based on epidemiology, clinical findings and positivity of immune response. The aim of the study was to characterize the OTB cases identified in Lisbon. METHODS: Retrospective study on OTB cases diagnosed in Lisbon from 2012 to 2015. The authors gathered data regarding demographic characteristics, diagnostic criteria, type of treatment as well as therapeutic results...
September 2018: Pulmonology
Ángel García-Barragán, José A Gutiérrez-Pabello, Edgar Alfonseca-Silva
Bovine tuberculosis, a re-emerging infectious disease caused by Mycobacterium bovis, can be transmitted to humans. Global prevalence of M. bovis in humans is underestimated and represents a serious public health risk in developing countries. In light of this situation, it is important to note that our understanding of the immunopathogenesis of human tuberculosis can be improved by studying this disease in the bovine model. Stimulation of the bovine innate immune system with calcitriol (1,25(OH)2D3) leads to an increase in bactericidal molecules involved in macrophage antimicrobial activity...
August 2018: Comparative Immunology, Microbiology and Infectious Diseases
Elsa du Bruyn, Nashied Peton, Hanif Esmail, Patrick J Howlett, Anna K Coussens, Robert J Wilkinson
PURPOSE OF REVIEW: Tuberculosis is the leading infectious cause of death worldwide, and HIV-1 the best recognized risk factor for active TB. This review focuses on immune complex formation; the interplay of type I and II interferon signaling; and T-cell activation in HIV-TB pathogenesis. RECENT FINDINGS: Circulating immune complexes and complement, and Fcγ signaling in whole blood act as early markers of TB disease in HIV-1-infected persons. HIV-1 is associated with a type I interferon response in whole blood, reducing the specificity of TB biomarkers dependent on type I and II interferon genes...
November 2018: Current Opinion in HIV and AIDS
Amira Refai, Sami Gritli, Mohamed-Ridha Barbouche, Makram Essafi
Tuberculosis, a human infectious disease caused by Mycobacterium tuberculosis ( M.tb ), is still a major cause of morbidity and mortality worldwide. The success of M.tb as a pathogen relies mainly on its ability to divert the host innate immune responses. One way by which M.tb maintains a persistent infection in a "silent" granuloma is to inhibit inflammation and induce an immunoregulatory phenotype in host macrophages (MΦs). However, M.tb effectors governing the switch of MΦs from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype remain to be determined...
2018: Frontiers in Cellular and Infection Microbiology
Charles Kyriakos Vorkas, Matthew F Wipperman, Kelin Li, James Bean, Shakti K Bhattarai, Matthew Adamow, Phillip Wong, Jeffrey Aubé, Marc Antoine Jean Juste, Vanni Bucci, Daniel W Fitzgerald, Michael S Glickman
Innate immune responses that control early Mtb infection are poorly understood, but understanding these responses may inform vaccination and immunotherapy strategies. Innate T cells that respond to conserved bacterial ligands such as mucosal-associated invariant T (MAIT) and γδ T cells are prime candidates to mediate these early innate responses but have not been examined in subjects who have been recently exposed to Mtb. We recruited a cohort living in the same household with an active tuberculosis (TB) case and examined the abundance and functional phenotypes of 3 innate T cell populations reactive to M...
October 4, 2018: JCI Insight
Olivier Van Der Meeren, Mark Hatherill, Videlis Nduba, Robert J Wilkinson, Monde Muyoyeta, Elana Van Brakel, Helen M Ayles, German Henostroza, Friedrich Thienemann, Thomas J Scriba, Andreas Diacon, Gretta L Blatner, Marie-Ange Demoitié, Michele Tameris, Mookho Malahleha, James C Innes, Elizabeth Hellström, Neil Martinson, Tina Singh, Elaine J Akite, Aisha Khatoon Azam, Anne Bollaerts, Ann M Ginsberg, Thomas G Evans, Paul Gillard, Dereck R Tait
BACKGROUND: A vaccine to interrupt the transmission of tuberculosis is needed. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya, South Africa, and Zambia. Human immunodeficiency virus (HIV)-negative adults 18 to 50 years of age with latent M. tuberculosis infection (by interferon-γ release assay) were randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart...
September 25, 2018: New England Journal of Medicine
Zoë M McLaren, Alana Sharp, Elizabeth Brouwer, Ananta Nanoo
Human immunodeficiency virus/Tuberculosis (HIV/TB) coinfection is particularly prevalent in South Africa, where TB has been the leading cause of death for more than a decade. The 2004-2008 national rollout of antiretroviral therapy (ART) provides a unique opportunity to examine the population-level impact of ART on the TB epidemic. We performed longitudinal regression analysis to follow the evolution of TB outcomes before and after the introduction of ART using a large data set from the National Health Laboratory Service...
October 1, 2018: American Journal of Tropical Medicine and Hygiene
Sang Kyun Ahn, Vanessa Tran, Andrea Leung, Mark Ng, Ming Li, Jun Liu
The live tuberculosis vaccine Mycobacterium bovis BCG (Bacille Calmette-Guérin) comprises a number of genetically distinct substrains. In BCG-Prague, phoP of the PhoP-PhoR two-component system is a pseudogene due to a single insertion mutation. We hypothesized that this mutation partially accounts for the low immunogenicity of BCG-Prague observed in the 1970s. In this study, we showed that complementation with the M. bovis allele of phoP restored BCG-Prague's immunogenicity. Furthermore, we showed that overexpression of the M...
September 1, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Hilte F Geerdes-Fenge, Micha Löbermann, Christoph J Hemmer, Orsolya Benedek, Emil C Reisinger
A 22-year-old HIV-negative man from Ghana was diagnosed with severe hemophagocytic lymphohistiocytosis (HLH) induced by multiorgan tuberculosis with peritoneal, hepatic, pericardial, myocardial, pleural, pulmonary, and bone manifestation. His body mass index was 12.9 m2 /kg. Bioptic material of a peritoneal biopsy grew M. tuberculosis, sensitive to all first-line antituberculous drugs. HLH resolved with antituberculous therapy, without additional anti-inflammatory therapy being given. The initial CT scan of his brain was normal...
September 26, 2018: Infection
Andrew J Olive, Christopher M Sassetti
Our understanding of the host response to infections has historically focused on "resistance" mechanisms that directly control pathogen replication. However, both pathogen effectors and antimicrobial immune pathways have the capacity to damage host tissue, and the ability to tolerate these insults can also be critical for host survival. These "tolerance" mechanisms may be equally as important as resistance to prevent disease in the context of a persistent infection, such as tuberculosis, when resistance mechanisms are ineffective and the pathogen persists in the tissue for long periods...
2018: Frontiers in Immunology
Garrett Teskey, Ruoqiong Cao, Hicret Islamoglu, Albert Medina, Chaya Prasad, Ramaa Prasad, Airani Sathananthan, Marcel Fraix, Selvakumar Subbian, Li Zhong, Vishwanath Venketaraman
Mycobacterium tuberculosis ( M. tb ), the causative bacterial agent responsible for tuberculosis (TB) continues to afflict millions of people worldwide. Although the human immune system plays a critical role in containing M. tb infection, elimination proves immensely more challenging. Consequently, there has been a worldwide effort to eradicate, and limit the spread of M. tb through the conventional use of first-line antibiotics. Unfortunately, with the emergence of drug resistant and multi-drug resistant strains of M...
2018: Frontiers in Immunology
Muhammad S Riaz, Anuvinder Kaur, Suha N Shwayat, Shahriar Behboudi, Uday Kishore, Ansar A Pathan
Mycobacterium tuberculosis , the causative agent of tuberculosis, is one of the leading causes of human deaths due to a single infectious agent. M. tuberculosis infection of the host initiates a local inflammatory response, resulting in the production of a range of inflammatory factors at the site of infection. These inflammatory factors may come in direct contact with M. tuberculosis and immune cells to activate different signaling pathways. One such factor produced in excess during inflammation is a phospholipid compound, Platelet Activating Factor C-16 (PAF C-16)...
2018: Frontiers in Microbiology
Nagender Rao Rameshwaram, Parul Singh, Sudip Ghosh, Sangita Mukhopadhyay
Lipid metabolism is thought to play a key role in the pathogenicity of several intracellular bacteria. Bacterial lipolytic enzymes hydrolyze lipids from the host cell to release free fatty acids which are used as an energy source and building blocks for the synthesis of cell envelope and also to modulate host immune responses. In this review, we discussed the role of lipid metabolism and lipolytic enzymes in the life cycle and virulence of Mycobacterium tuberculosis and other intracellular bacteria. The lipolytic enzymes appear to be potential candidates for developing novel therapeutics by targeting lipid metabolism for controlling M...
September 2018: Future Microbiology
Tan N Doan, Pengxing Cao, Theophilus I Emeto, James M McCaw, Emma S McBryde
Short-course regimens for multi-drug resistant tuberculosis (MDR-TB) are urgently needed. Limited data suggest that the new drug, bedaquiline (BDQ), may have the potential to shorten MDR-TB treatment to less than six months when used in conjunction with standard anti-TB drugs. However, the feasibility of BDQ in shortening MDR-TB treatment duration remains to be established. Mathematical modelling provides a platform to investigate different treatment regimens and predict their efficacy. We developed a mathematical model to capture the immune response to TB inside a human host environment...
September 24, 2018: Antimicrobial Agents and Chemotherapy
Stefania Fontana, Maria Pacciarini, Mery Boifava, Roberta Pellesi, Barbara Casto, Michele Gastaldelli, Heike Koehler, Nicola Pozzato, Francesco Casalinuovo, M Beatrice Boniotti
There is currently an increased interest in the use of serological approaches in combination with traditional cell-mediated immunity-based techniques to improve the detection of tuberculosis (TB)-infected animals. In the present study, we developed and validated two different serological TB-detection assays using four antigens, MPB70, MPB83, ESAT6 and CFP10, and the tuberculin PPDb. A conventional multi-antigen TB-ELISA method and a novel TB multiplex test, based on Luminex technology, were developed to detect antibodies to multiple antigen targets...
September 21, 2018: Journal of Microbiological Methods
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