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https://www.readbyqxmd.com/read/28526681/adoptive-transfer-of-phosphoantigen-specific-%C3%AE-%C3%AE-t-cell-subset-attenuates-mycobacterium-tuberculosis-infection-in-nonhuman-primates
#1
Arwa Qaqish, Dan Huang, Crystal Y Chen, Zhuoran Zhang, Richard Wang, Shengpu Li, Enzhuoa Yang, Yang Lu, Michelle H Larsen, William R Jacobs, Lixia Qian, James Frencher, Ling Shen, Zheng W Chen
The dominant Vγ2Vδ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γδ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28515464/systems-immunology-of-diabetes-tuberculosis-comorbidity-reveals-signatures-of-disease-complications
#2
Cesar A Prada-Medina, Kiyoshi F Fukutani, Nathella Pavan Kumar, Leonardo Gil-Santana, Subash Babu, Flávio Lichtenstein, Kim West, Shanmugam Sivakumar, Pradeep A Menon, Vijay Viswanathan, Bruno B Andrade, Helder I Nakaya, Hardy Kornfeld
Comorbid diabetes mellitus (DM) increases tuberculosis (TB) risk and adverse outcomes but the pathological interactions between DM and TB remain incompletely understood. We performed an integrative analysis of whole blood gene expression and plasma analytes, comparing South Indian TB patients with and without DM to diabetic and non-diabetic controls without TB. Luminex assay of plasma cytokines and growth factors delineated a distinct biosignature in comorbid TBDM in this cohort. Transcriptional profiling revealed elements in common with published TB signatures from cohorts that excluded DM...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28510418/conjugation-reaction-with-8-arm-peg-markedly-improves-the-immunogenicity-of-mycobacterium-tuberculosis-cfp10-tb10-4-fusion-protein
#3
Xiaowei Sun, Weili Yu, Quanhai Pang, Tao Hu
Mycobacterium tuberculosis (Mtb) is a serious fatal pathogen responsible for tuberculosis (TB). Effective vaccination is highly desired for immunoprotection against Mtb infection. CFP10 and TB10.4 are two important immunodominant Mtb-secreted protein antigens, which suffer from poor immunogenicity. Thus, an antigen delivery system and adjuvants are needed to improve the immunogenicity of the two proteins. CFP10 and TB10.4 are two Mtb-secreted immunodominant protein antigens. A CFP10-TB10.4 fusion protein (CT) was used as the antigen...
May 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28487695/regulatory-t-cells-and-pro-inflammatory-responses-predominate-in-children-with-tuberculosis
#4
Elizabeth Whittaker, Mark Nicol, Heather J Zar, Beate Kampmann
BACKGROUND: Following infection with Mycobacterium tuberculosis (M.tb), children are more susceptible to develop disease particularly extrapulmonary disease than adults. The exact mechanisms required for containment of M.tb are not known, but would be important to identify correlates of protection. OBJECTIVE: To comprehensively analyze key immune responses to mycobacteria between HIV-negative children with extrapulmonary TB (EPTB) compared to children with pulmonary TB (PTB) or healthy controls...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28483404/mycobacteria-specific-cytokine-responses-as-correlates-of-treatment-response-in-active-and-latent-tuberculosis
#5
Vanessa Clifford, Marc Tebruegge, Christel Zufferey, Susie Germano, Ben Forbes, Lucy Cosentino, Emma McBryde, Damon Eisen, Roy Robins-Browne, Alan Street, Justin Denholm, Nigel Curtis
OBJECTIVES: A biomarker indicating successful tuberculosis (TB) therapy would assist in determining appropriate length of treatment. This study aimed to determine changes in mycobacteria-specific antigen-induced cytokine biomarkers in patients receiving therapy for latent or active TB, to identify biomarkers potentially correlating with treatment success. METHODS: A total of 33 adults with active TB and 36 with latent TB were followed longitudinally over therapy...
May 5, 2017: Journal of Infection
https://www.readbyqxmd.com/read/28475642/mhc-ib-molecule-qa-1-presents-mycobacterium-tuberculosis-peptide-antigens-to-cd8-t-cells-and-contributes-to-protection-against-infection
#6
Yao Bian, Shaobin Shang, Sarah Siddiqui, Jie Zhao, Simone A Joosten, Tom H M Ottenhoff, Harvey Cantor, Chyung-Ru Wang
A number of nonclassical MHC Ib molecules recognizing distinct microbial antigens have been implicated in the immune response to Mycobacterium tuberculosis (Mtb). HLA-E has been identified to present numerous Mtb peptides to CD8+ T cells, with multiple HLA-E-restricted cytotoxic T lymphocyte (CTL) and regulatory T cell lines isolated from patients with active and latent tuberculosis (TB). In other disease models, HLA-E and its mouse homolog Qa-1 can act as antigen presenting molecules as well as regulators of the immune response...
May 5, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28472067/the-effect-of-current-schistosoma-mansoni-infection-on-the-immunogenicity-of-a-candidate-tb-vaccine-mva85a-in-bcg-vaccinated-adolescents-an-open-label-trial
#7
Anne Wajja, Dennison Kizito, Beatrice Nassanga, Angela Nalwoga, Joyce Kabagenyi, Simon Kimuda, Ronald Galiwango, Gertrude Mutonyi, Samantha Vermaak, Iman Satti, Jaco Verweij, Edridah Tukahebwa, Stephen Cose, Jonathan Levin, Pontiano Kaleebu, Alison M Elliott, Helen McShane
INTRODUCTION: Helminth infection may affect vaccine immunogenicity and efficacy. Adolescents, a target population for tuberculosis booster vaccines, often have a high helminth burden. We investigated effects of Schistosoma mansoni (Sm) on the immunogenicity and safety of MVA85A, a model candidate tuberculosis vaccine, in BCG-vaccinated Ugandan adolescents. METHODS: In this phase II open label trial we enrolled 36 healthy, previously BCG-vaccinated adolescents, 18 with no helminth infection detected, 18 with Sm only...
May 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28454648/the-siglec14-null-allele-is-associated-with-mycobacterium-tuberculosis-and-bcg-induced-clinical-and-immunologic-outcomes
#8
Andrew D Graustein, David J Horne, Jerry J Fong, Flavio Schwarz, Heather C Mefford, Glenna J Peterson, Richard D Wells, Munyaradzi Musvosvi, Muki Shey, Willem A Hanekom, Mark Hatherill, Thomas J Scriba, Nguyen Thuy Thuong Thuong, Nguyen Thi Hoang Mai, Maxine Caws, Nguyen Duc Bang, Sarah J Dunstan, Guy E Thwaites, Ajit Varki, Takashi Angata, Thomas R Hawn
Humans exposed to Mycobacterium tuberculosis (Mtb) have variable susceptibility to tuberculosis (TB) and its outcomes. Siglec-5 and Siglec-14 are members of the sialic-acid binding lectin family that regulate immune responses to pathogens through inhibitory (Siglec-5) and activating (Siglec-14) domains. The SIGLEC14 coding sequence is deleted in a high proportion of individuals, placing a SIGLEC5-like gene under the expression of the SIGLEC14 promoter (the SIGLEC14 null allele) and causing expression of a Siglec-5 like protein in monocytes and macrophages...
May 2017: Tuberculosis
https://www.readbyqxmd.com/read/28450725/heat-shock-protein70-is-implicated-in-modulating-nf-%C3%AE%C2%BAb-activation-in-alveolar-macrophages-of-patients-with-active-pulmonary-tuberculosis
#9
Chun-Hua Wang, Pai-Chien Chou, Fu-Tsai Chung, Horng-Chyuan Lin, Kuo-Hsiung Huang, Han-Pin Kuo
Heat shock proteins (HSPs) have been shown to modulate NF-κB activation. It is unknown whether HSP70 plays a role in modulating NF-κB-mediated pro-inflammatory cytokines released from alveolar macrophage (AM) of patients with active pulmonary tuberculosis (TB). Peripheral blood monocytes (PBMs) and AM were sampled from nineteen active TB patients and 14 healthy individuals. HSP70 expression was 3-fold higher in AMs of active TB patients than normal subjects, and declined after receiving 3-month anti-TB treatment...
April 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28448542/diminished-plasma-levels-of-common-%C3%AE-chain-cytokines-in-pulmonary-tuberculosis-and-reversal-following-treatment
#10
Nathella Pavan Kumar, Vaithilingam V Banurekha, Dina Nair, Subash Babu
BACKGROUND: The immune response to tuberculosis (TB) is T cell dependent. T cells are the major facilitators of protection and effector functions with CD4+ T cells being the most important players, followed by CD8+ T cells. The common γ-chain cytokines IL-2, IL-7, IL-15, and IL-21 play a vital role in peripheral T cell growth and survival. However, the role of common γ-chain cytokines in pulmonary TB (PTB) is poorly understood. AIM AND METHODS: To examine the association of circulating common γ-chain cytokines with TB disease or infection, we examined the systemic levels of IL-2, IL-7, IL-15, and IL-21 in individuals with PTB, latent TB (LTB) or no TB infection (NTB)...
2017: PloS One
https://www.readbyqxmd.com/read/28446902/modulation-of-macrophage-responses-by-cmx-a-fusion-protein-composed-of-ag85c-mpt51-and-hspx-from-mycobacterium-tuberculosis
#11
Adeliane C da Costa, Danilo P de Resende, Bruno de P O Santos, Karina F Zoccal, Lúcia H Faccioli, André Kipnis, Ana P Junqueira-Kipnis
Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is a vaccine used to prevent tuberculosis (TB). Due to the poor protection conferred by BCG in adults, new, more effective formulations have been developed. A recombinant BCG vaccine expressing the CMX fusion protein Ag85c_MPT51_HspX (rBCG-CMX) induced Th1 and Th17 responses and provided better protection than BCG. It has been shown that Mycobacterium smegmatis expressing CMX also induces better protection than BCG and is a strong macrophage activator. The aim of the present study was to evaluate macrophage activation by the recombinant CMX fusion protein and by rBCG-CMX and to evaluate their ability to generate vaccine-specific immune responses...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28438554/interleukin-17f-and-interleukin-6-gene-polymorphisms-in-asian-indian-patients-with-takayasu-arteritis
#12
Debashish Danda, Ruchika Goel, Sumita Danda, Hindhumathi Mohan, George Joseph, Jayakanthan Kabeerdoss, Swapan K Nath
OBJECTIVES: To assess genetic association between single nucleotide polymorphisms (SNPs) in genes encoding T-helper cytokines and Takayasu Arteritis (TA) susceptibility in Asian Indian population. METHODS: In Phase-1, the genomic DNA of 120 TA patients and 119 healthy controls were genotyped for SNPs rs1800795 (interleukin (IL)-6), rs763780 (IL-17F), rs1800871, rs1800872, rs1800896 (IL-10) and rs1800468, rs1800469, rs1800470 (transforming growth factor-β). Allele frequencies between cases and controls were compared using chi-squared test and also reassessed empirically (pe) by 10,000 permutations...
April 22, 2017: Human Immunology
https://www.readbyqxmd.com/read/28436493/an-attenuated-mycobacterium-tuberculosis-clinical-strain-with-a-defect-in-esx-1-secretion-induces-minimal-host-immune-responses-and-pathology
#13
Helena Strand Clemmensen, Niels Peter Hell Knudsen, Erik Michael Rasmussen, Jessica Winkler, Ida Rosenkrands, Ahmad Ahmad, Troels Lillebaek, David R Sherman, Peter Lawætz Andersen, Claus Aagaard
Although Mycobacterium tuberculosis (M.tb) DK9897 is an attenuated strain, it was isolated from a patient with extrapulmonary tuberculosis and vaccination with a subunit vaccine (H56) induced poor protection against it. Both attenuation and lack of protection are because M.tb DK9897 cannot secrete the EsxA virulence factor nor induce a host response against it. Genome sequencing identified a frameshift mutation in the eccCa1 gene. Since the encoded EccCa1 protein provides energy for ESX-1 secretion, it suggested a defect in the ESX-1 type VII secretion system...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28430824/suppressors-of-cytokine-signaling-in-tuberculosis
#14
Shih-Wei Lee, Chi-Wei Liu, Jia-Ying Hu, Li-Mei Chiang, Chih-Pin Chuu, Lawrence Shih-Hsin Wu, Yung-Hsi Kao
Tuberculosis (TB), a global disease mainly infected by Mycobacterium tuberculosis, remains leading public health problem worldwide. Suppressors of cytokine signaling (SOCSs) play important roles in the protection against microbial infection. However, the relationship between members of the SOCS family and tuberculosis infection remains unclear. Using peripheral blood mononuclear cells, we investigated the mRNA expression profiles of SOCS subfamilies among active TB, latent tuberculosis infection (LTBI), and healthy individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28412202/the-immunosuppressive-effects-of-a-novel-recombinant-lipq-rv2485c-protein-of-mycobacterium-tuberculosis-on-human-macrophage-cell-lines
#15
Anjani Kumar, Manisha, Gurkamaljit Kaur Sangha, Anju Shrivastava, Jagdeep Kaur
Mycobacterium tuberculosis (MTB), an intracellular pathogen, still represents a major global health challenge. A number of mycobacterial macromolecules have been shown to target biological processes within host macrophages; however, the exact mechanism for the majority of these host pathogen interactions is still poorly understood. Moreover, the lipid metabolic pathway is one of the most important physiologic pathways that plays a vital role in the survival and infection of Mycobacterium tuberculosis. In present study, we investigated the effect of rLipQ from Mycobacterium tuberculosis H37Rv on macrophage functions in vitro...
April 12, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28399967/type-1-polarised-dendritic-cells-are-a-potent-immunogen-against-mycobacterium-tuberculosis
#16
Y Satake, Y Nakamura, M Kono, H Hozumi, T Nagata, K Tsujimura, N Enomoto, T Fujisawa, N Inui, T Fujiyama, Y Tokura, T Matsui, K Yokomura, M Shirai, H Hayakawa, T Suda
OBJECTIVE: Application of immunotherapy using dendritic cells (DCs) is considered an effective treatment strategy against persistent Mycobacterium tuberculosis infection. With the goal of developing improved therapeutic vaccination strategies for patients with tuberculosis (TB), we tested the ability of ex vivo-generated DCs to induce an effective TB antigen-specific type-1 immune response. METHODS: Monocyte-derived DCs from TB patients were induced to mature using a 'standard' cytokine cocktail (interleukin [IL] 1β, tumour necrosis factor alpha [TNF-α], IL-6 and prostaglandin E2) or a type 1-polarised DC (DC1) cocktail (IL-1β, TNF-α, interferon [IFN] α, IFN-γ and polyinosinic:polycytidylic acid), and were loaded with the established TB antigen 6-kDa early secretory antigenic target protein (ESAT-6)...
May 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28398535/diagnostic-utility-of-new-equation-for-active-tuberculosis-based-on-parameters-of-interferon-%C3%AE-release-assay
#17
You La Jeon, Min-Jeong Kim, Woo-In Lee, Myeong Hee Kim, So Young Kang
Background: We derived a new equation to include interferon-γ (IFN-γ) levels in the QuantiFERON-Gold In-Tube (QFT-GIT) assay to discriminate active tuberculosis (ATB) infection from latent TB, and compared the diagnostic performance of the QFT-GIT assay and the new equation. Methods: From January 2013 through May 2015, we retrospectively enrolled 159 and 408 patients with and without ATB, respectively, in this study. Discriminant analysis was performed to derive an equation to distinguish the ATB group from the non-ATB group...
April 8, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/28387740/protective-effect-of-bicyclol-on-anti-tuberculosis-drug-induced-liver-injury-in-rats
#18
Xin Liu, Manman Zhao, Jiaqi Mi, Hui Chen, Li Sheng, Yan Li
The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB) drug-induced liver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral administration of an anti-TB drug once a day for 30 days. Liver injury was evaluated by biochemical and histopathological examinations. Lipid peroxidation, mitochondrial function, and the activity of antioxidants were measured by spectrophotometric methods...
April 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28386077/an-assay-system-for-point-of-care-diagnosis-of-tuberculosis-using-commercially-manufactured-pcb-technology
#19
Daniel Evans, Konstantinos I Papadimitriou, Louise Greathead, Nikolaos Vasilakis, Panagiotis Pantelidis, Peter Kelleher, Hywel Morgan, Themistoklis Prodromakis
Rapid advances in clinical technologies, detection sensitivity and analytical throughput have delivered a significant expansion in our knowledge of prognostic and diagnostic biomarkers in many common infectious diseases, such as Tuberculosis (TB). During the last decade, a significant number of approaches to TB diagnosis have been attempted at Point-of-Care (PoC), exploiting a large variation of techniques and materials. In this work, we describe an electronics-based Enzyme-Linked ImmunoSorbent Assay (eELISA), using a Lab-on-a-Printed Circuit Board (LoPCB) approach, for TB diagnosis based on cytokine detection...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28385088/plants-in-our-combating-strategies-against-mycobacterium-tuberculosis-progress-made-and-obstacles-met
#20
Vivek Kumar Gupta, M Madhan Kumar, Deepa Bisht, Anupam Kaushik
CONTEXT: Traditionally used plants for treating chest-related problems/tuberculosis (TB) have not been evaluated in detail and hence a thorough study is needed in this regard. This knowledge may find application in developing new anti-TB drugs. OBJECTIVE: This article elaborates on studying the activity of medicinal plants against different forms of Mycobacterium tuberculosis (Mtb) using different model strains, in vitro and ex vivo assays for studying the tuberculocidal activity and discusses the results from different studies on the activity against different forms of Mtb and human immunodeficiency virus-tuberculosis (HIV-TB) co-infection...
December 2017: Pharmaceutical Biology
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