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https://www.readbyqxmd.com/read/29325881/rv2204c-rv0753c-and-rv0009-antigens-specific-t-cell-responses-in-latent-and-active-tb-a-flow-cytometry-based-analysis
#1
Balaji Pathakumari, Santhi Devasundaram, Prabhavathi Maddineni, Alamelu Raja
High global prevalence of latent TB infection (LTBI) is a key challenge in distinguishing patients with active pulmonary TB (PTB) from those with LTBI. The functional profile of CD4+ and CD8+ T cell cytokines produced as a response to Mycobacterium tuberculosis antigens vary during the course of tuberculosis (TB) infection. We evaluated antigen-specific CD4+ and CD8+ T cell cytokine response after overnight in vitro stimulation of peripheral blood with mycobacterial antigens ESAT-6, CFP-10, Rv2204c, Rv0753c and Rv0009 by flow cytometry...
December 6, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/29321075/a-phase-i-open-label-trial-on-the-safety-and-immunogenicity-of-the-adjuvanted-tuberculosis-subunit-vaccine-h1-ic31%C3%A2-in-people-living-in-a-tb-endemic-area
#2
Jemal Hussein, Martha Zewdie, Lawrence Yamuah, Ahmed Bedru, Markos Abebe, Alemnew F Dagnew, Menberework Chanyalew, Asfawesen G Yohannes, Jemal Ahmed, Howard Engers, T Mark Doherty, Peter Bang, Ingrid Kromann, Søren T Hoff, Abraham Aseffa
BACKGROUND: H1/IC31® is a tuberculosis (TB) subunit vaccine candidate consisting of the fusion protein of Ag85B and ESAT-6 (H1) formulated with the IC31® adjuvant. Previous trials have reported on the H1/IC31® vaccine in M. tuberculosis (Mtb)-naïve, BCG-vaccinated and previously Mtb-infected individuals. In this trial, conducted between December 2008 and April 2010, the safety and immunogenicity of H1/IC31® was assessed in participants living in Ethiopia - a highly TB-endemic area...
January 10, 2018: Trials
https://www.readbyqxmd.com/read/29311492/innate-immunity-mediated-by-dendritic-cells-macrophages-plays-a-central-role-in-the-early-period-in-tumor-treatment-using-gene-of-mycobacterium-tuberculosis-antigen
#3
Takahiro Ushigusa, Yoshiyuki Koyama, Tomoko Ito, Kenichi Watanabe, James K Chambers, Aya Hasegawa, Kazuyuki Uchida, Ryoji Kanegi, Shingo Hatoya, Toshio Inaba, Kikuya Sugiura
By using a complex of DNA, polyethylenimine and chondroitin sulfate, the in vivo transfection of early secretory antigenic target-6 (ESAT-6) gene into tumor cells was found to cause significant suppression of the tumor growth. In order to apply the method in clinical cancer treatment in dogs and cats, mechanisms underlying the suppressive effects were investigated in a tumor-bearing mouse model. The transfection efficiency was only about 10%, but the transfection of ESAT-6 DNA nevertheless induced systemic immune responses against ESAT-6...
January 1, 2018: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29311240/potential-immunological-biomarkers-for-detection-of-mycobacterium-tuberculosis-infection-in-endemic-setting-ethiopia
#4
Takele Teklu, Kwon Keehwan, Biniam Wondale, Milkessa HaileMariam, Mengistu Legesse, Girmay Medhin, Aboma Zewude, Rembert Pieper, Gobena Ameni
Accurate diagnosis and early treatment of tuberculosis (TB) and latent TB infection (LTBI) are vital to prevent and control TB. The lack of specific biomarkers hinders these efforts. This study's purpose was to screen immunological markers that discriminate M. tuberculosis (Mtb) infection outcomes in an endemic setting of Ethiopia. Whole blood from 90 participants was stimulated using the ESAT-6/CFP-10 antigen cocktail. The interferon-γ (IFN-γ)-based QuantiFERON diagnostic test was used to distinguish between LTBI and uninfected control cases...
January 8, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29310595/potential-of-dosr-and-rpf-antigens-from-mycobacterium-tuberculosis-to-discriminate-between-latent-and-active-tuberculosis-in-a-tuberculosis-endemic-population-of-medellin-colombia
#5
Leonar Arroyo, Diana Marín, Kees L M C Franken, Tom H M Ottenhoff, Luis F Barrera
BACKGROUND: Tuberculosis (TB) remains one of the most deadly infectious diseases. One-third to one-fourth of the human population is estimated to be infected with Mycobacterium tuberculosis (Mtb) without showing clinical symptoms, a condition called latent TB infection (LTBI). Diagnosis of Mtb infection is based on the immune response to a mixture of mycobacterial antigens (PPD) or to Mtb specific ESAT-6/CFP10 antigens (IGRA), highly expressed during the initial phase of infection. However, the immune response to PPD and IGRA antigens has a low power to discriminate between LTBI and PTB...
January 8, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29250493/determination-of-lipoprotein-z-specific-iga-in-tuberculosis-and-latent-tuberculosis-infection
#6
Jia-Ni Xiao, Yanqing Xiong, Yingying Chen, Yang-Jiong Xiao, Ping Ji, Yong Li, Shu-Jun Wang, Guo-Ping Zhao, Qi-Jian Cheng, Shui-Hua Lu, Ying Wang
Tuberculosis (TB) remains one of the most severe infectious diseases. It is still of paramount importance to establish more accurate, rapid, and efficient diagnostic methods. Since infection with Mycobacterium tuberculosis (M. tb) is largely mediated through the respiratory tract, IgA responses against mycobacterial proteins are worthy of investigation for their potential clinical utility. In this study, the IgA response targeting lipoprotein Z (LppZ) was determined by using a homemade ELISA with plasma of TB patients (N = 125), LTBI individuals (N = 92), healthy controls (HCs) (N = 165), as well as TB patients undergoing anti-TB treatment (N = 9)...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29249639/t-cells-primed-by-live-mycobacteria-versus-a-tuberculosis-subunit-vaccine-exhibit-distinct-functional-properties
#7
Thomas Lindenstrøm, Albanus Moguche, Mie Damborg, Else Marie Agger, Kevin Urdahl, Peter Andersen
Despite inducing strong T cell responses, Mycobacterium tuberculosis (Mtb) infection fails to elicit protective immune memory. As such latently infected or successfully treated Tuberculosis (TB) patients are not protected against recurrent disease. Here, using a mouse model of aerosol Mtb infection, we show that memory immunity to H56/CAF01 subunit vaccination conferred sustained protection in contrast to the transient natural immunity conferred by Mtb infection. Loss of protection to re-infection in natural Mtb memory was temporally linked to an accelerated differentiation of ESAT-6- and to a lesser extent, Ag85B-specific CD4 T cells in both the lung parenchyma and vasculature...
December 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29230248/a-concise-review-on-the-use-of-mesenchymal-stem-cells-in-cell-sheet-based-tissue-engineering-with-special-emphasis-on-bone-tissue-regeneration
#8
REVIEW
A Cagdas Yorukoglu, A Esat Kiter, Semih Akkaya, N Lale Satiroglu-Tufan, A Cevik Tufan
The integration of stem cell technology and cell sheet engineering improved the potential use of cell sheet products in regenerative medicine. This review will discuss the use of mesenchymal stem cells (MSCs) in cell sheet-based tissue engineering. Besides their adhesiveness to plastic surfaces and their extensive differentiation potential in vitro, MSCs are easily accessible, expandable in vitro with acceptable genomic stability, and few ethical issues. With all these advantages, they are extremely well suited for cell sheet-based tissue engineering...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29215597/application-of-pharmacokinetics-modelling-to-predict-human-exposure-of-a-cationic-liposomal-subunit-antigen-vaccine-system
#9
Raj K S Badhan, Swapnil Khadke, Yvonne Perrie
The pharmacokinetics of a liposomal subunit antigen vaccine system composed of the cationic lipid dimethyldioctadecylammonium bromide (DDA) and the immunostimulatory agent trehalose 6,6-dibehenate (TDB) (8:1 molar ratio) combined with the Ag85B-ESAT-6 (H1) antigen were modelled using mouse in-vivo data. Compartment modelling and physiologically based pharmacokinetics (PBPK) were used to predict the administration site (muscle) and target site (lymph) temporal concentration profiles and factors governing these...
December 7, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/29210987/prophylactic-sublingual-immunization-with-mycobacterium-tuberculosis-subunit-vaccine-incorporating-the-natural-killer-t-cell-agonist-alpha-galactosylceramide-enhances-protective-immunity-to-limit-pulmonary-and-extra-pulmonary-bacterial-burden-in-mice
#10
Arshad Khan, Shailbala Singh, Gloria Galvan, Chinnaswamy Jagannath, K Jagannadha Sastry
Infection by Mycobacterium tuberculosis (Mtb) remains a major global concern and the available Bacillus Calmette-Guerin (BCG) vaccine is poorly efficacious in adults. Therefore, alternative vaccines and delivery strategies focusing on Mtb antigens and appropriate immune stimulating adjuvants are needed to induce protective immunity targeted to the lungs, the primary sites of infections and pathology. We present here evidence in support of mucosal vaccination by the sublingual route in mice using the subunit Mtb antigens Ag85B and ESAT-6 adjuvanted with the glycolipid alpha-galactosylceramide (α-GalCer), a potent natural killer T (NKT) cell agonist...
December 6, 2017: Vaccines
https://www.readbyqxmd.com/read/29198784/pathogenesis-of-tuberculosis-and-other-mycobacteriosis
#11
Pere-Joan Cardona
The evolution between Mycobacterium tuberculosis infection and active tuberculosis is multifactorial and involves different biological scales. The synthesis of ESAT-6 or the induction of alveolar macrophage necrosis are key, but to understand it, it is necessary to consider the dynamics of endogenous and exogenous reinfection, drainage of lung parenchyma and respiratory mechanics, local fibrosis processes and blood supply. Paradoxically, the immune response generated by the infection is highly protective (90%) against active tuberculosis, although as it is essentially based on the proliferation of Th1 lymphocytes, it cannot prevent reinfection...
November 30, 2017: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/29189087/diagnostic-usefulness-of-the-quantiferon-tb-gold-in-tube-test-qft-git-for-tuberculous-vertebral-osteomyelitis
#12
Sungim Choi, Kyung Hwa Jung, Hyo-Ju Son, Seung Hyun Lee, Jung Min Hong, Min Chul Kim, Min Jae Kim, Yong Pil Chong, Heungsup Sung, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Sung-Han Kim
BACKGROUND: Interferon (IFN)-γ-releasing assay for diagnosing tuberculosis (TB) has shown promise; however, there are only a few reports on usefulness of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) for diagnosing TB vertebral osteomyelitis. METHODS: All patients presenting at a tertiary hospital between January 2010 and July 2016 with suspected TB vertebral osteomyelitis were retrospectively enrolled to evaluate the diagnostic performance of QFT-GIT. We used QFT-GIT to measure the IFN-γ response to ESAT-6, CFP-10 and TB7...
November 30, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/29180415/whib6-regulation-of-esx-1-gene-expression-is-controlled-by-a-negative-feedback-loop-in-mycobacterium-marinum
#13
Rachel E Bosserman, Tiffany T Nguyen, Kevin G Sanchez, Alexandra E Chirakos, Micah J Ferrell, Cristal R Thompson, Matthew M Champion, Robert B Abramovitch, Patricia A Champion
ESX (ESAT-6 system) export systems play diverse roles across mycobacterial species. Interestingly, genetic disruption of ESX systems in different species does not result in an accumulation of protein substrates in the mycobacterial cell. However, the mechanisms underlying this observation are elusive. We hypothesized that the levels of ESX substrates were regulated by a feedback-control mechanism, linking the levels of substrates to the secretory status of ESX systems. To test this hypothesis, we used a combination of genetic, transcriptomic, and proteomic approaches to define export-dependent mechanisms regulating the levels of ESX-1 substrates in Mycobacterium marinum WhiB6 is a transcription factor that regulates expression of genes encoding ESX-1 substrates...
November 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29180292/nlrp3-inflammasome-activation-by-mycobacterial-esat-6-and-dsrna-in-intraocular-tuberculosis
#14
Soumyava Basu, Benjamin Fowler, Nagaraj Kerur, Kristine B Arnvig, Narsing A Rao
The molecular basis of intraocular tuberculosis (TB) is not well understood. In this study, we investigated the role of two constituents of viable Mycobacterium tuberculosis - Early Secreted Antigenic Target-6 (ESAT-6), and mycobacterial RNA- in inflammasome activation in the retinal pigment epithelium (RPE) - a key site of inflammation in intraocular TB. We found that ESAT-6 induced caspase-1 activation and inflammasome priming in mouse RPE cells, significantly more in wild-type than in Tlr2/3/4/7/9-/-, Myd88-/- and Nlrp3-/- RPE cells...
November 24, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29161328/use-of-quantiferon%C3%A2-tb-gold-in-tube-culture-supernatants-for-measurement-of-antibody-responses
#15
Simon G Kimuda, Irene Andia-Biraro, Moses Egesa, Bernard S Bagaya, John G Raynes, Jonathan Levin, Alison M Elliott, Stephen Cose
QuantiFERON®-TB Gold in-tube (QFT-GIT) supernatants may be important samples for use in assessment of anti-tuberculosis (TB) antibodies when only limited volumes of blood can be collected and when a combination of antibody and cytokine measurements are required. These analytes, when used together, may also have the potential to differentiate active pulmonary TB (APTB) from latent TB infection (LTBI). However, few studies have explored the use of QFT-GIT supernatants for investigations of antibody responses...
2017: PloS One
https://www.readbyqxmd.com/read/29145844/development-and-evaluation-of-an-interferon-gamma-assay-for-the-diagnosis-of-tuberculosis-in-red-deer-experimentally-infected-with-mycobacterium-bovis
#16
María Ángeles Risalde, Jobin Thomas, Iker Sevilla, Miriam Serrano, Jose Antonio Ortíz, Joseba Garrido, Mercedes Domínguez, Lucas Domínguez, Christian Gortázar, Jose Francisco Ruíz-Fons
BACKGROUND: Red deer (Cervus elaphus) is regarded as an epidemiologically relevant host for Mycobacterium bovis (M. bovis) and closely related members of the Mycobacterium tuberculosis complex that cause animal tuberculosis (TB). The standard antemortem screening test for the detection of TB in deer is the intradermal tuberculin skin test, but the detection of interferon-gamma (IFNγ) produced by white blood cells exposed to M. bovis antigens can be used as an alternative or supplemental assay in most TB eradication/control programs...
November 16, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29134265/deletion-of-the-%C3%AE-propeller-protein-gene-rv1057-reduces-esat-6-secretion-and-intracellular-growth-of-mycobacterium-tuberculosis
#17
Jiafang Fu, Gongli Zong, Peipei Zhang, Yuanxin Gu, Guangxiang Cao
Rv1057 is the only β-propeller protein in Mycobacterium tuberculosis, but its biological function is still unclear. In this study, we generated a deletion mutant of Rv1057 (D1057) in the virulent M. tuberculosis strain H37Rv and examined the characteristics of the mutant in vitro and in macrophages. We found that deletion of Rv1057 reduces secretion of the major virulence factor ESAT-6 and ESAT-6 stops in the cell envelope fraction during secretion, although ESAT-6 levels were similar in lysates of the mutant and control strains...
November 13, 2017: Current Microbiology
https://www.readbyqxmd.com/read/29125874/pulmonary-immune-responses-to-mycobacterium-tuberculosis-in-exposed-individuals
#18
Christian Herzmann, Martin Ernst, Christoph Lange, Steffen Stenger, Stefan H E Kaufmann, Norbert Reiling, Tom Schaberg, Lize van der Merwe, Jeroen Maertzdorf
BACKGROUND: Blood based Interferon-(IFN)-γ release assays (IGRAs) have a poor predictive value for the development of tuberculosis. This study aimed to investigate the correlation between IGRAs and pulmonary immune responses in tuberculosis contacts in Germany. METHODS: IGRAs were performed on bronchoalveolar lavage (BAL) cells and peripheral blood from close healthy contacts of patients with culturally confirmed tuberculosis. Cellular BAL composition was determined by flow cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/29119205/secretome-profile-analysis-of-multidrug-resistant-monodrug-resistant-and-drug-susceptible-mycobacterium-tuberculosis
#19
Chanyanuch Putim, Narumon Phaonakrop, Janthima Jaresitthikunchai, Ratikorn Gamngoen, Khajornsak Tragoolpua, Sorasak Intorasoot, Usanee Anukool, Chayada Sitthidet Tharincharoen, Ponrut Phunpae, Chatchai Tayapiwatana, Watchara Kasinrerk, Sittiruk Roytrakul, Bordin Butr-Indr
The emergence of drug-resistant tuberculosis has generated great concern in the control of tuberculosis and HIV/TB patients have established severe complications that are difficult to treat. Although, the gold standard of drug-susceptibility testing is highly accurate and efficient, it is time-consuming. Diagnostic biomarkers are, therefore, necessary in discriminating between infection from drug-resistant and drug-susceptible strains. One strategy that aids to effectively control tuberculosis is understanding the function of secreting proteins that mycobacteria use to manipulate the host cellular defenses...
November 8, 2017: Archives of Microbiology
https://www.readbyqxmd.com/read/29101404/autoreactive-t-cells-in-immunopathogenesis-of-tb-associated-uveitis
#20
Ravichandra Tagirasa, Shaifaly Parmar, Manas R Barik, Satish Devadas, Soumyava Basu
Purpose: Intraocular inflammation in tuberculosis-associated uveitis (TBU) is usually widespread, and responds unpredictably to treatment. Herein, we analyze the intraocular T-cell response in TBU for its surface phenotype, antigenic specificity, and functional characteristics to explain the above observations. Methods: We isolated T cells from vitreous humor samples of patients with TBU and non-TB uveitis (controls). These were directly stained for surface markers CD4, CD8, CD45RO, CD45RA, CCR7, as well as intracellular cytokines IFN-γ, TNF-α, and IL-17 and analyzed on flow cytometry...
November 1, 2017: Investigative Ophthalmology & Visual Science
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