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https://www.readbyqxmd.com/read/28634479/whole-blood-profiling-of-bacillus-calmette-gu%C3%A3-rin-induced-trained-innate-immunity-in-infants-identifies-epidermal-growth-factor-il-6-platelet-derived-growth-factor-ab-bb-and-natural-killer-cell-activation
#1
Steven G Smith, Johanneke Kleinnijenhuis, Mihai G Netea, Hazel M Dockrell
Vaccination of infants with bacillus Calmette-Guérin (BCG) activates both the innate and adaptive arms of the immune response. The antimycobacterial effects of these responses most likely account for the ability of BCG to protect against childhood forms of tuberculosis (TB). There is also evidence for a heterologous protective effect of BCG vaccination against TB-unrelated mortality in low birth weight infants. A possible mechanism of action of this effect, the induction of trained innate immunity, has been demonstrated when cells from BCG-vaccinated adults are restimulated in vitro with non-related microbial stimuli...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28620588/immunogenicity-and-protective-efficacy-of-a-fusion-protein-tuberculosis-vaccine-combining-five-esx-family-proteins
#2
Zhi-Hao Xiang, Rui-Feng Sun, Chen Lin, Fu-Zeng Chen, Jun-Tao Mai, Yu-Xiao Liu, Zi-Yan Xu, Lu Zhang, Jun Liu
One strategy to develop the next generation of tuberculosis vaccines is to construct subunit vaccines based on T cell antigens. In this study, we have evaluated the vaccine potential of a fusion protein combining EsxB, EsxD, EsxG, EsxU, and EsxM of Mycobacterium tuberculosis (M. tb). This recombinant protein, named BM, was expressed in and purified from Escherichia coli. Immunization of C57BL/6 mice with purified BM protein formulated in Freund's incomplete adjuvant induced the production of Th1 cytokines (IFN-γ, TNF, and IL-2) and multifunctional CD4(+) T cells...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28610780/analysis-of-transcription-factors-micrornas-and-cytokines-involved-in-t-lymphocyte-differentiation-in-patients-with-tuberculosis-after-directly-observed-treatment-short-course
#3
Nancy Elizabeth Corral-Fernández, Juan Diego Cortes-García, Rivas-Santiago Bruno, Silvia Romano-Moreno, Susanna E Medellín-Garibay, Martín Magaña-Aquino, Raúl A Salazar-González, Roberto González-Amaro, Diana Patricia Portales-Pérez
Tuberculosis (Tb) is an infectious disease in which the immune system plays an important role. MicroRNAs are involved in the development and maintenance of CD4 + T lymphocyte subpopulations. miR-326 regulates the differentiation to Th17 cells and miR-29 correlates with the Th1 response. The aim of this study was to determine the role of microRNAs, Transcription Factors, and cytokines in Th differentiation before and after the directly observed treatment short-course (DOTS). Peripheral blood mononuclear cells and serum from Tb patients were collected at times 0 (before therapy), 2 (after the intensive phase), and 6 months (after the holding phase)...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28598206/a-novel-in-vitro-human-granuloma-model-of-sarcoidosis-and-latent-tb-infection
#4
Elliott D Crouser, Peter White, Evelyn Guirado Caceres, Mark W Julian, Audrey C Papp, Landon W Locke, Wolfgang Sadee, Larry S Schlesinger
Many aspects of pathogenic granuloma formation are poorly understood requiring new relevant laboratory models that represent the complexity (genetics and diversity) of human disease. To address this need, we developed an in vitro model of granuloma formation using human peripheral blood mononuclear cells (PBMCs) derived from patients with active sarcoidosis, latent tuberculosis (TB) infection (LTBI), or normal healthy controls. PBMCs were incubated for 7 days with uncoated polystyrene beads or beads coated with purified protein derivative (PPD) or human serum albumin (HSA)...
June 9, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28594940/the-introduction-of-mesenchymal-stromal-cells-induces-different-immunological-responses-in-the-lungs-of-healthy-and-m-tuberculosis-infected-mice
#5
Tatiana Nenasheva, Alexander Nikolaev, Daniar Diykanov, Anna Sukhanova, Evgenii Tcyganov, Alexander Panteleev, Irina Bocharova, Yana Serdyuk, Leonid Nezlin, Tatiana Radaeva, Nikolai Adrianov, Yuri Rubtsov, Irina Lyadova
Mesenchymal stromal cells (MSC) have strong immunomodulatory properties and therefore can be used to control inflammation and tissue damage. It was suggested recently that MSC injections can be used to treat multi-drug resistant tuberculosis (TB). However, MSC trafficking and immunomodulatory effects of MSC injections during Mycobacterium tuberculosis (Mtb) infection have not been studied. To address this issue we have analyzed MSC distribution in tissues and local immunological effects of MSC injections in Mtb infected and uninfected mice...
2017: PloS One
https://www.readbyqxmd.com/read/28588287/identification-and-evaluation-of-the-novel-immunodominant-antigen-rv2351c-from-mycobacterium-tuberculosis
#6
Xuezhi Wang, Shuangshuang Chen, Yongjuan Xu, Huajun Zheng, Tongyang Xiao, Yuqing Li, Xing Chen, Mingxiang Huang, Haifeng Zhang, Xijing Fang, Yi Jiang, Machao Li, Haican Liu, Kanglin Wan
There is an urgent need for new immunodominant antigens to improve the diagnosis of tuberculosis (TB) and the efficacy of the TB vaccine to control the disease worldwide. In this study, we evaluated the diagnostic potential of a novel Mycobacterium tuberculosis (MTB)-specific antigen, Rv2351c, from region of difference (RD) 7 of the MTB genome, and investigated the potency of the vaccine by identifying its immunological function in human and animal immunological experiments. Twenty T-cell epitopes were identified using TEpredict and prediction tools from the Immune Epitope Database and Analysis Resource...
June 7, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28588268/optimisation-of-a-murine-splenocyte-mycobacterial-growth-inhibition-assay-using-virulent-mycobacterium-tuberculosis
#7
Christina Jensen, Line Lindebo Holm, Erik Svensson, Claus Aagaard, Morten Ruhwald
In the absence of a validated correlate of protection or robust animal models for human tuberculosis, Mycobacterial growth inhibition assays (MGIAs) aim to assess vaccines ability to inhibit mycobacterial growth in-vitro. We optimised a reproducible murine splenocyte MGIA based on in-vitro infection with virulent Mycobacterium tuberculosis (M.tb) Erdman. We identified splenocyte viability as a problem in state-of-art MGIA protocols, which can be improved by simple changes in culture conditions (viability increase from 21% to 46% at last day of culture)...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588103/mycobacteriumtuberculosis-rv3615c-is-a-highly-immunodominant-antigen-and-specifically-inducespotent-th1-type-immune-responses-in-tuberculosis-pleurisy
#8
Jiangping Li, Juan Shen, Suihua Lao, Xiaomin Li, Jie Liu, Changyou Wu
T-cell responses have been demonstrated essential for preventing M.tb infection. The Th1-cytokines produced by T cells, such as INF-γ, IL-2 and TNF-α, not only limit the invasion of M.tb but also eliminate the pathogen at site of infection. BCG is known to induce Th1-type responses but the protection is inadequate. Identification of immunogenic components in addition to those expressed in BCG and induction of a broad spectrum of Th1-type responses provide options for generating sufficient adaptive immunity...
June 6, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28584007/t-cell-derived-il-10-impairs-host-resistance-to-mycobacterium-tuberculosis-infection
#9
Lúcia Moreira-Teixeira, Paul S Redford, Evangelos Stavropoulos, Nico Ghilardi, Craig L Maynard, Casey T Weaver, Ana Paula Freitas do Rosário, Xuemei Wu, Jean Langhorne, Anne O'Garra
Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, is a leading cause of mortality and morbidity, causing ∼1.5 million deaths annually. CD4(+) T cells and several cytokines, such as the Th1 cytokine IFN-γ, are critical in the control of this infection. Conversely, the immunosuppressive cytokine IL-10 has been shown to dampen Th1 cell responses to M. tuberculosis infection impairing bacterial clearance. However, the critical cellular source of IL-10 during M. tuberculosis infection is still unknown...
June 5, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28570642/mycobacterium-tuberculosis-subverts-negative-regulatory-pathways-in-human-macrophages-to-drive-immunopathology
#10
Patience T Brace, Liku B Tezera, Magdalena K Bielecka, Toby Mellows, Diana Garay, Shuye Tian, Lucinda Rand, Justin Green, Sanjay Jogai, Andrew J Steele, Timothy M Millar, Tilman Sanchez-Elsner, Jon S Friedland, Christopher G Proud, Paul T Elkington
Tuberculosis remains a global pandemic and drives lung matrix destruction to transmit. Whilst pathways driving inflammatory responses in macrophages have been relatively well described, negative regulatory pathways are less well defined. We hypothesised that Mycobacterium tuberculosis (Mtb) specifically targets negative regulatory pathways to augment immunopathology. Inhibition of signalling through the PI3K/AKT/mTORC1 pathway increased matrix metalloproteinase-1 (MMP-1) gene expression and secretion, a collagenase central to TB pathogenesis, and multiple pro-inflammatory cytokines...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28562756/concordance-between-ifn%C3%AE-gene-874-a-t-polymorphism-and-interferon-%C3%AE-expression-in-a-tb-endemic-indigenous-setting
#11
Zaida Araujo, Andrea Palacios, Rubén Biomon, Bruno Rivas-Santiago, Carmen Judith Serrano, Leonor Enciso-Moreno, Juan Ernesto López-Ramos, Albina Wide, Juan Carlos Jiménez, Carlos Fernández de Larrea, José Antonio Enciso-Moreno
INTRODUCTION: Interferon-γ (IFN-γ) plays a crucial role in resistance to mycobacterial diseases; accordingly, variants of the gene encoding this cytokine may be associated with elevated risk of contracting pulmonary tuberculosis (TB). METHODS: Blood samples were collected from 135 Warao indigenous individuals with newly diagnosed sputum culture-positive TB. Of these, 24 were diagnosed with active tuberculosis (ATB). The study comprised 111 participants, who were grouped as follows: 1) 14 tuberculin skin test (TST)-positive Warao indigenous individuals and 4 that were QuantiFERON-TB?Gold In-Tube (QFT-IT) test-positive, collectively comprising the latent TB infection group (LTBI), n = 18), and 2) healthy controls who were QFT-IT- and TST-negative, comprising the control group (CTRL, n = 93)...
March 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28558065/prediabetes-is-associated-with-the-modulation-of-antigen-specific-th1-tc1-and-th17-tc17-responses-in-latent-mycobacterium-tuberculosis-infection
#12
Nathella Pavan Kumar, Kadar Moideen, Chandrakumar Dolla, Paul Kumaran, Subash Babu
Type 2 diabetes mellitus (DM) is associated with the down modulation of Th1, Th2 and Th17 responses in latent Mycobacterium tuberculosis infection but the role of prediabetes (PDM) in this setting is not well understood. To examine the role of CD4+ and CD8+ T cell cytokines in latent tuberculosis (LTB) with coincident PDM, we studied the baseline, mycobacterial, control antigen and mitogen-stimulated T cell cytokine responses in LTB individuals with (LTB-PDM; n = 20) or without (LTB-NDM; n = 20) concomitant prediabetes...
2017: PloS One
https://www.readbyqxmd.com/read/28543817/influence-of-diabetes%C3%A2-mellitus-on-the-immunity-to-human-tuberculosis
#13
REVIEW
Nathella Pavan Kumar, Subash Babu
Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis, with development of DM pandemic in countries where tuberculosis (TB) is also endemic. Understanding the impact of DM on TB and the determinants of co-morbidity is essential in responding to this growing public health problem with improved therapeutic approaches. Despite the clinical and public health significance posed by the dual burden of TB and DM, little is known about the immunological and biochemical mechanisms of susceptibility...
May 22, 2017: Immunology
https://www.readbyqxmd.com/read/28540757/association-of-tuberculosis-status-with-neurologic-disease-and-immune-response-in-htlv-1-infection
#14
Anselmo Souza, Natália Carvalho, Yuri Neves, Silvane Braga Santos, Maria de Lourdes Bastos, Sergio Arruda, Eduardo Martins Netto, Marshall Glesby, Edgar Carvalho
The human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 infected individuals have increased susceptibility to Mycobacterium tuberculosis infection but the influence of tuberculosis on the course of HTLV-1 infection is unknown. The aim of this study was to evaluate the influence of tuberculosis on immunological, virologic, and neurologic features of HTLV-1 infection. This is a retrospective analysis of individuals enrolled in a cohort study from an HTLV-1 clinic who were evaluated for past or latent tuberculosis and classified clinically as HTLV-1 carriers, probable HAM/TSP and definite HAM/TSP...
May 25, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28537661/effect-of-urinary-trypsin-inhibitor-on-inflammatory-cytokines-and-organ-function-in-patients-with-cardiopulmonary-bypass
#15
H-Y Xu, X-S Rong, D-P Wang, S-Y Jiang, Z-D Zang, W Xia, F Zhang, J Yan
OBJECTIVE: This research is to study the effect of urinary trypsin inhibitor (UTI) on inflammatory cytokines and organ function in patients with cardiopulmonary bypass. PATIENTS AND METHODS: From February 2015 to February 2016, 40 patients that had undergone cardiopulmonary bypass surgery in our hospital were selected and randomly divided into the observation group and the control group with 20 patients in each group. Patients in the control group were intravenously injected with 5000 U/kg normal saline during the operation and 5000 U/kg•d-1 at 1-3 days postoperatively, while the patients in the observation group received intravenous injection of the same amount of UTI at pre-operation (T0), post-anesthesia (T1), after aortic opening (T2), after cardiopulmonary bypass 4h (T3), 8h (T4), 24h (T5), 48h (T6), and 72h (T7)...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28536578/expansion-of-cd25-negative-forkhead-box-p3-positive-t-cells-during-hiv-and-mycobacterium-tuberculosis-infection
#16
Matías T Angerami, Guadalupe V Suarez, María B Vecchione, Natalia Laufer, Diego Ameri, Graciela Ben, Hector Perez, Omar Sued, Horacio Salomón, María F Quiroga
Tuberculosis (TB) and HIV alter the immune system, and coinfected (HIV-TB) individuals usually present deregulations of T-lymphocytic immune response. We previously observed an increased frequency of "unconventional" CD4(+)CD25(-)FoxP3(+) Treg (uTreg) population during HIV-TB disease. Therefore, we aimed to explore the phenotype and function of uTreg and conventional CD4(+)CD25(+)FoxP3(+) Treg subsets (cTreg) in this context. We evaluated the expression of CD39, programmed cell death protein 1 (PD1), glucocorticoid-induced tumor necrosis factor receptor (GITR), and the effector/memory distribution by flow cytometry in cTreg and uTreg...
2017: Frontiers in Immunology
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
#17
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...
June 15, 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
#18
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
#19
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. A CFP10-TB10.4 fusion protein (CT) was used as the antigen in the present study. Conjugation of 4-6 CT molecules in one entity with 8-arm polyethylene glycol (PEG) acted as an antigen delivery system...
June 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28487695/regulatory-t-cells-and-pro-inflammatory-responses-predominate-in-children-with-tuberculosis
#20
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
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