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https://www.readbyqxmd.com/read/29163427/antimycobacterial-and-anti-inflammatory-mechanisms-of-baicalin-via-induced-autophagy-in-macrophages-infected-with-mycobacterium-tuberculosis
#1
Qingwen Zhang, Jinxia Sun, Yuli Wang, Weigang He, Lixin Wang, Yuejuan Zheng, Jing Wu, Ying Zhang, Xin Jiang
Tuberculosis (TB) remains a leading killer worldwide among infectious diseases and the effective control of TB is still challenging. Autophagy is an intracellular self-digestion process which has been increasingly recognized as a major host immune defense mechanism against intracellular microorganisms like Mycobacterium tuberculosis (Mtb) and serves as a key negative regulator of inflammation. Clinically, chronic inflammation surrounding Mtb can persist for decades leading to lung injury that can remain even after successful treatment...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29161328/use-of-quantiferon%C3%A2-tb-gold-in-tube-culture-supernatants-for-measurement-of-antibody-responses
#2
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/29151578/th1-cytokines-true-functional-signatures-for-protective-immunity-against-tb
#3
REVIEW
Gucheng Zeng, Guoliang Zhang, Xinchun Chen
The lack of an effective preventative vaccine against tuberculosis (TB) presents a great challenge to TB control. Since it takes an extremely long time to accurately determine the protective efficacy of TB vaccines, there is a great need to identify the surrogate signatures of protection to facilitate vaccine development. Unfortunately, antigen-specific Th1 cytokines that are currently used to evaluate the protective efficacy of the TB vaccine, do not align with the protection and failure of TB vaccine candidates in clinical trials...
November 20, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29147487/a-study-on-the-immune-response-induced-by-a-dna-vaccine-encoding-mtb32c-hbha-antigen-of-mycobacterium-tuberculosis
#4
Roghayeh Teimourpour, Hadi Peeridogaheh, Amir Teimourpour, Mohsen Arzanlou, Zahra Meshkat
Objectives: Tuberculosis (TB) has still remained a global health issue. One third of the world's population is infected with tuberculosis and the current BCG vaccine has low efficiency; hence, it is necessary to develop a new vaccine against TB. The aim of the current study was to evaluate the efficiency of a novel DNA vaccine encoding Mtb32C-HBHA antigen in inducing specific immune responses against Mycobacterium tuberculosis. Materials and Methods: A DNA plasmid vaccine expressing Mtb32C-HBHA fusion protein was constructed and its ability in protein expression was examined by RT-PCR and Western blot methods...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29135655/neutrophil-activation-and-enhanced-release-of-granule-products-in-hiv-tb-immune-reconstitution-inflammatory-syndrome
#5
Justine K Nakiwala, Naomi F Walker, Collin R Diedrich, William Worodria, Graeme Meintjes, Robert J Wilkinson, Harriet Mayanja-Kizza, Robert Colebunders, Luc Kestens, Katalin A Wilkinson, David M Lowe
BACKGROUND: Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) remains incompletely understood. Neutrophils are implicated in tuberculosis pathology but detailed investigations in TB-IRIS are lacking. We sought to further explore the biology of TB-IRIS and in particular the role of neutrophils. SETTING: Two observational, prospective cohort studies in HIV/TB co-infected patients starting antiretroviral therapy, one to analyze gene expression and subsequently one to explore neutrophil biology...
November 6, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29125874/pulmonary-immune-responses-to-mycobacterium-tuberculosis-in-exposed-individuals
#6
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/29124751/detailed-characterization-of-human-mycobacterium-tuberculosis-specific-hla-e-restricted-cd8-t-cells
#7
Teresa Prezzemolo, Krista E van Meijgaarden, Kees Lmc Franken, Nadia Caccamo, Francesco Dieli, Tom Hm Ottenhoff, Simone A Joosten
HLA-E presented antigens are interesting targets for vaccination given HLA-Es' essentially monomorphic nature. We have shown previously that Mycobacterium tuberculosis (Mtb) peptides are presented by HLA-E to CD8(+) effector T-cells, but the precise phenotype and functional capacity of these cells remains poorly characterized. We have developed and utilized in this study a new protocol combining HLA-E tetramer with intracellular staining for cytokines, transcription factors and cytotoxic molecules to characterize these cells in depth...
November 9, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29101404/autoreactive-t-cells-in-immunopathogenesis-of-tb-associated-uveitis
#8
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
https://www.readbyqxmd.com/read/29100034/down-regulation-of-notch-signaling-pathway-reverses-the-th1-th2-imbalance-in-tuberculosis-patients
#9
Qifeng Li, Hui Zhang, Liang Yu, Chao Wu, Xinhui Luo, He Sun, Jianbing Ding
Th1/Th2 imbalance to Th2 is of significance in the peripheral immune responses in Tuberculosis (TB) development. However, the mechanisms for Th1/Th2 imbalance are still not well determined. Notch signaling pathway is involved in the peripheral T cell activation and effector cell differentiation. However, whether it affects Th1/Th2 imbalance in TB patients is still not known. Here, we used γ-secretase inhibitor (DAPT) to treat the peripheral blood mononuclear cells (PBMCs) from healthy people or individuals with latent or active TB infection in vitro, respectively...
October 28, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29075255/il-17-production-from-t-helper-17-mucosal-associated-invariant-t-and-%C3%AE-%C3%AE-cells-in-tuberculosis-infection-and-disease
#10
Felicity Coulter, Amy Parrish, Declan Manning, Beate Kampmann, Joseph Mendy, Mathieu Garand, David M Lewinsohn, Eleanor M Riley, Jayne S Sutherland
IL-17-producing cells have been shown to be important in the early stages of Mycobacterium tuberculosis (Mtb) infection in animal models. However, there are very little data on the role of IL-17 in human studies of tuberculosis (TB). We recruited TB patients and their highly exposed contacts who were further categorized based on results from an IFN-γ-release assay (IGRA): (1) IGRA positive (IGRA(+)) at recruitment (latently TB infected), (2) IGRA negative (IGRA(-)) at recruitment and 6 months [non-converters (NC)], and (3) IGRA(-) at recruitment and IGRA(+) at 6 months (converters)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29053932/the-patterns-of-in-vitro-cell-death-and-inflammatory-cytokines-induced-by-distinct-bcg-vaccine-strains-are-differentially-induced-in-human-mononuclear-cells
#11
C Ponte, M Hacker, M Moraes, L Castello-Branco, F Silva, P Antas
Tuberculosis (TB) remains among the world's leading cause of mortality. For its control, studies of TB vaccines are needed. Since live-attenuated Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only TB vaccine currently in use, studies on the protective role of BCG are required. In this study, we analyzed host cells purified directly from whole blood of human immunodeficiency virus (HIV)-negative volunteers, comprising adult healthy donors (HD) and neonates (umbilical cord bloods, UCB), with the aim to directly compare in vitro immune responses with distinct BCG strains in human mononuclear cells...
October 20, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29051764/polyfunctional-cd4-t-cells-as-targets-for-tuberculosis-vaccination
#12
REVIEW
Deborah A Lewinsohn, David M Lewinsohn, Thomas J Scriba
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of morbidity and mortality worldwide, despite the widespread use of the only licensed vaccine, Bacille Calmette Guerin (BCG). Eradication of TB will require a more effective vaccine, yet evaluation of new vaccine candidates is hampered by lack of defined correlates of protection. Animal and human studies of intracellular pathogens have extensively evaluated polyfunctional CD4(+) T cells producing multiple pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-2) as a possible correlate of protection from infection and disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29050777/multiplex-analysis-of-plasma-cytokines-chemokines-showing-different-immune-responses-in-active-tb-patients-latent-tb-infection-and-healthy-participants
#13
Xiangyang Yao, Yongliang Liu, Yang Liu, Wei Liu, Zhizhong Ye, Chao Zheng, Shengxiang Ge
Interferon gamma release assays (IGRAs) have been widely used to diagnose Mycobacterium tuberculosis (MTB) infection. However, IGRAs cannot discriminate between active TB patients and latent TB infection (LTBI), and the sensitivity of IGRAs for MTB infection is suboptimal. Here, we analyzed cytokines/chemokines in MTB antigen-stimulated and -unstimulated plasma samples to identify host biomarkers that are associated with active TB and MTB infection. Active TB patients, subjects with LTBI and healthy participants were recruited...
December 2017: Tuberculosis
https://www.readbyqxmd.com/read/29042992/timosaponin-b-iii-exhibits-antidepressive-activity-in-a-mouse-model-of-postpartum-depression-by-the-regulation-of-inflammatory-cytokines-bndf-signaling-and-synaptic-plasticity
#14
Xiao-Li Zhang, Lin Wang, Li Xiong, Feng-Hua Huang, Han Xue
The aim of this study was to investigate the antidepressive effects of timosaponin B-III (TB-III) and the underlying mechanism. A postpartum depression (PPD) mouse model was established by the administration of dexamethasone sodium phosphate during pregnancy. Mice with PPD were assigned to the following groups: Model, fluoxetine and high, medium and low doses of TB-III. Post-parturient mice without PPD served as a normal control group. To examine the effect of TB-III, mice were treated with TB-III, then forced swimming tests (FSTs) and tail suspension tests (TSTs) were performed to evaluate depression...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29034213/a-promising-listeria-vectored-vaccine-induces-th1-type-immune-responses-and-confers-protection-against-tuberculosis
#15
Yuelan Yin, Kai Lian, Dan Zhao, Chengwu Tao, Xiang Chen, Weijun Tan, Xiaobo Wang, Zhengzhong Xu, Maozhi Hu, Yan Rao, Xiaohui Zhou, Zhiming Pan, Xiaoming Zhang, Xin'an Jiao
Deaths associated with tuberculosis (TB) is rising and accounted for 1.4 million deaths in 2015 many of which were due to drug-resistant bacteria. Vaccines represent an important medical intervention, but the current Bacilli Calmette-Guerin (BCG) vaccine is not ideal for the protection of teenagers and adults. Therefore, a safe and effective vaccine is urgently needed. In this study, we designed a novel vaccine using an attenuated Listeria monocytogenes strain carrying fusion antigen FbpB-ESAT-6 (rLM) and characterized its safety and protective efficacy against Mycobacterium tuberculosis (M...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29029171/effect-of-hiv-on-the-frequency-and-number-of-mycobacterium-tuberculosis-specific-cd4-t-cells-in-blood-and-the-airways-in-latent-tuberculosis-infection
#16
Rubina Bunjun, Catherine Riou, Andreia P Soares, Narjis Thawer, Tracey L Müller, Agano Kiravu, Zekarias Ginbot, Tolu Oni, Rene Goliath, Barbara Kalsdorf, Florian von Groote-Bidlingmaier, Willem Hanekom, Gerhard Walzl, Robert J Wilkinson, Wendy A Burgers
HIV-1 infection substantially increases the risk of developing tuberculosis (TB). There is extensive depletion of Mycobacterium tuberculosis (M.tuberculosis)-specific CD4+ T cells in blood in early HIV infection, but little is known about responses in the lungs at this stage. Given that mucosal organs are a principal target for HIV-mediated CD4 destruction, we investigated M.tuberculosis-specific responses in bronchoalveolar lavage (BAL), in persons with latent TB infection and untreated HIV-1 co-infection with preserved CD4 counts...
October 5, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29017282/plasma-cytokine-predictors-of-tuberculosis-recurrence-in-antiretroviral-treated-human-immunodeficiency-virus-infected-individuals-from-durban-south-africa
#17
Aida Sivro, Lyle R McKinnon, Nonhlanhla Yende-Zuma, Santhana Gengiah, Natasha Samsunder, Salim S Abdool Karim, Kogieleum Naidoo
Background: Immune correlates of tuberculosis (TB) risk in populations infected with human immunodeficiency virus (HIV) remain understudied, despite HIV being associated with a high burden of TB disease. Here we describe plasma cytokine correlates of TB recurrence in a well-characterized cohort of HIV-infected individuals on antiretroviral therapy (ART) with a history of prior TB cure. Methods: Study participants were drawn from a prospective cohort study initiated at the conclusion of a randomized clinical trial in which individuals presented with untreated HIV infection and active pulmonary TB...
September 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28991491/nanowire-aptasensors-for-electrochemical-detection-of-cell-secreted-cytokines
#18
Ying Liu, Ali Rahimian, Sergiy Krylyuk, Tam Vu, Bruno Crulhas, Gulnaz Stybayeva, Meruyert Imanbekova, Dong-Sik Shin, Albert Davydov, Alexander Revzin
Cytokines are small proteins secreted by immune cells in response to pathogens/infections; therefore, these proteins can be used in diagnosing infectious diseases. For example, release of a cytokine interferon (IFN)-γ from T-cells is used for blood-based diagnosis of tuberculosis (TB). Our lab has previously developed an atpamer-based electrochemical biosensor for rapid and sensitive detection of IFN-γ. In this study, we explored the use of silicon nanowires (NWs) as a way to create nanostructured electrodes with enhanced sensitivity for IFN-γ...
October 9, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28985739/a-lipidated-peptide-of-mycobacterium-tuberculosis-resuscitates-the-protective-efficacy-of-bcg-vaccine-by-evoking-memory-t-cell-immunity
#19
Pradeep K Rai, Sathi Babu Chodisetti, Weiguang Zeng, Sajid Nadeem, Sudeep K Maurya, Susanta Pahari, Ashok K Janmeja, David C Jackson, Javed N Agrewala
BACKGROUND: The current BCG vaccine induces only short-term protection against Mycobacterium tuberculosis (Mtb), suggesting its failure to generate long-lasting memory T cells. Previously, we have demonstrated that a self-adjuvanting peptide of Mtb (L91), successfully generated enduring memory Th1 cells. Consequently, we investigated if L91 was able to recuperate BCG potency in perpetuating the generation of memory T cells and protection against Mtb infected mice. METHODS: In the present study, we evaluated the potency of a self adjuvanting Mtb peptide vaccine L91 in invigorating BCG immune response against Mtb in mice...
October 6, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28978810/interleukin-17-limits-hypoxia-inducible-factor-1%C3%AE-and-development-of-hypoxic-granulomas-during-tuberculosis
#20
Racquel Domingo-Gonzalez, Shibali Das, Kristin L Griffiths, Mushtaq Ahmed, Monika Bambouskova, Radha Gopal, Suhas Gondi, Marcela Muñoz-Torrico, Miguel A Salazar-Lezama, Alfredo Cruz-Lagunas, Luis Jiménez-Álvarez, Gustavo Ramirez-Martinez, Ramón Espinosa-Soto, Tamanna Sultana, James Lyons-Weiler, Todd A Reinhart, Jesus Arcos, Maria de la Luz Garcia-Hernandez, Michael A Mastrangelo, Noor Al-Hammadi, Reid Townsend, Joan-Miquel Balada-Llasat, Jordi B Torrelles, Gilla Kaplan, William Horne, Jay K Kolls, Maxim N Artyomov, Javier Rangel-Moreno, Joaquín Zúñiga, Shabaana A Khader
Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark of pulmonary tuberculosis (TB) is the formation of hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, hypoxic necrotic granulomas are associated with increased disease severity and provide a niche for drug-resistant Mtb. However, the host immune responses that promote the development of hypoxic TB granulomas are not well described. Using a necrotic Mtb mouse model, we show that loss of Mtb virulence factors, such as phenolic glycolipids, decreases the production of the proinflammatory cytokine IL-17 (also referred to as IL-17A)...
October 5, 2017: JCI Insight
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