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https://www.readbyqxmd.com/read/28216183/safety-and-immunogenicity-of-the-novel-h4-ic31-tuberculosis-vaccine-candidate-in-bcg-vaccinated-adults-two-phase-i-dose-escalation-trials
#1
Maria Norrby, Timo Vesikari, Lars Lindqvist, Markus Maeurer, Raija Ahmed, Shahnaz Mahdavifar, Sean Bennett, J Bruce McClain, Barbara M Shepherd, Daner Li, David A Hokey, Ingrid Kromann, Søren T Hoff, Peter Andersen, Adriëtte W de Visser, Simone A Joosten, Tom H M Ottenhoff, Jan Andersson, Susanna Brighenti
BACKGROUND: Novel vaccine strategies are required to provide protective immunity in tuberculosis (TB) and prevent development of active disease. We investigated the safety and immunogenicity of a novel TB vaccine candidate, H4:IC31 (AERAS-404) that is composed of a fusion protein of M. tuberculosis antigens Ag85B and TB10.4 combined with an IC31® adjuvant. METHODS: BCG-vaccinated healthy subjects were immunized with various antigen (5, 15, 50, 150μg) and adjuvant (0, 100, 500nmol) doses of the H4:IC31 vaccine (n=106) or placebo (n=18) in two randomized, double-blind, placebo-controlled phase I studies conducted in a low TB endemic setting in Sweden and Finland...
February 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28215633/tlr-4-mirna-32-5p-fstl1-signaling-regulates-mycobacterial-survival-and-inflammatory-responses-in-mycobacterium-tuberculosis-infected-macrophages
#2
Zhi-Min Zhang, Ai-Rong Zhang, Min Xu, Jun Lou, Wei-Qiang Qiu
Macrophages play a pivotal role in host immune response against mycobacterial infection, which is tightly modulated by multiple factors, including microRNAs. The purpose of the present study was to investigate the biological function and potential mechanism of miR-32-5p in human macrophages during Mycobacterium tuberculosis (M.tb) infection. The results demonstrated that miR-32-5p was robustly enhanced in THP-1 and U937 cells in response to M.tb infection. TLR-4 signaling was required for upregulation of miR-32-5p induced by M...
February 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28193909/rv2299c-a-novel-dendritic-cell-activating-antigen-of-mycobacterium-tuberculosis-fused-esat-6-subunit-vaccine-confers-improved-and-durable-protection-against-the-hypervirulent-strain-hn878-in-mice
#3
Han-Gyu Choi, Seunga Choi, Yong Woo Back, Seungwha Paik, Hye-Soo Park, Woo Sik Kim, Hongmin Kim, Seung Bin Cha, Chul Hee Choi, Sung Jae Shin, Hwa-Jung Kim
Understanding functional interactions between DCs and antigens is necessary for achieving an optimal and desired immune response during vaccine development. Here, we identified and characterized protein Rv2299c (heat-shock protein 90 family), which effectively induced DC maturation. The Rv2299c-maturated DCs showed increased expression of surface molecules and production of proinflammatory cytokines. Rv2299c induced these effects by binding to TLR4 and stimulating the downstream MyD88-, MAPK- and NF-κB-dependent signaling pathways...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178208/effector-mechanisms-of-neutrophils-within-the-innate-immune-system-in-response-to-mycobacterium-tuberculosis-infection
#4
REVIEW
Eric Warren, Garrett Teskey, Vishwanath Venketaraman
Neutrophils have a significant yet controversial role in the innate immune response to Mycobacterium tuberculosis (M. tb) infection, which is not yet fully understood. In addition to neutrophils' well-known effector mechanisms, they may also help control infection of M. tb through the formation of neutrophil extracellular traps (NETs), which are thought to further promote the killing of M. tb by resident alveolar macrophages. Cytokines such as IFN-γ have now been shown to serve an immunomodulatory role in neutrophil functioning in conjunction to its pro-inflammatory function...
February 7, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28177354/dietary-supplementation-with-tributyrin-prevented-weaned-pigs-from-growth-retardation-and-lethal-infection-via-modulation-of-inflammatory-cytokines-production-ileal-expression-and-intestinal-acetate-fermentation
#5
Y Gu, Y Song, H Yin, S Lin, X Zhang, L Che, Y Lin, S Xu, B Feng, D Wu, Z Fang
Weanling pigs, with an underdeveloped intestine and immature immune system, are usually subjected to depressed feed intake, growth retardation, and postweaning diarrhea. The aim of this study was to determine 1) the growth response of weaned pigs to supplemental tributyrin (TB) and 2) the potential effects and mechanisms of TB in modulating immune responses of lipopolysaccharide (LPS)-challenged piglets. A total of 240 piglets (Duroc × Large White × Landrace) were weaned at 21 d of age to a control (basal diet), supplemented with antibiotics (AB; +AB), supplemented with TB (+TB), or with supplemental AB and TB (+AB+TB) diets, with 10 replicate pens (6 piglets/pen) per diet...
January 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28167672/anthelmintic-therapy-modifies-the-systemic-and-mycobacterial-antigen-stimulated-cytokine-profile-in-helminth-latent-mycobacterium-tuberculosis-co-infection
#6
Rajamanickam Anuradha, Saravanan Munisankar, Yukthi Bhootra, Chandrakumar Dolla, Paul Kumaran, Thomas B Nutman, Subash Babu
Helminth infections are known to modulate cytokine responses in latent tuberculosis (LTB). However, very few studies have examined whether this modulation is reversible upon anthelmintic therapy. We measured the systemic and mycobacterial (TB) - antigen-stimulated levels of Type 1, Type 2, Type 17 and regulatory cytokines in individuals with LTB and with or without coexistent Strongyloides stercoralis (Ss) infection before and after anthelmintic therapy. Our data reveal that individuals with LTB and coexistent Ss infection have significantly lower levels of systemic and TB antigen-stimulated Type 1 (IFNγ, TNFα and IL-2) and Type 17 (IL-17A and/or IL-17F) cytokines and significantly higher levels of systemic but not TB antigen-stimulated Type 2 (IL-4 and IL-5) and regulatory (TGFβ) cytokines...
February 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28161459/peptide-microarray-based-characterization-of-antibody-responses-to-host-proteins-after-bacille-calmette-gu%C3%A3-rin-vaccination
#7
REVIEW
Davide Valentini, Martin Rao, Lalit Rane, Sayma Rahman, Rebecca Axelsson-Robertson, Rainer Heuchel, Matthias Löhr, Daniel Hoft, Susanna Brighenti, Alimuddin Zumla, Markus Maeurer
BACKGROUND: Bacille Calmette-Guérin (BCG) is the world's most widely distributed vaccine, used against tuberculosis (TB), in cancer immunotherapy, and in autoimmune diseases due to its immunomodulatory properties. To date, the effect of BCG vaccination on antibody responses to host proteins has not been reported. High-content peptide microarrays (HCPM) offer a unique opportunity to gauge specific humoral immune responses. METHODS: The sera of BCG-vaccinated healthy adults were tested on a human HCPM platform (4953 randomly selected epitopes of human proteins) to detect specific immunoglobulin gamma (IgG) responses...
February 2, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28161108/rv0774c-an-iron-stress-inducible-extracellular-esterase-is-involved-in-immune-suppression-associated-with-altered-cytokine-and-tlr2-expression
#8
Arbind Kumar, Sukh Mahendra Singh, Ranvir Singh, Jagdeep Kaur
Tuberculosis, one of the leading cause of death from infectious diseases, is caused by Mycobacterium tuberculosis. The genome of M. tuberculosis has been sequenced and nearly 40% of the whole genome sequence was categorized as hypothetical. Rv0774c was annotated as membrane exported hypothetical protein in TB database. In silico analysis revealed that Rv0774c is a paralog of PE-PGRS multi gene family with 100 aa N-terminal domain similar to PE domain of PE-PGRS proteins. Its C-terminal domain is quite different from PGRS domain, having characteristic lipase signature GXSXG & HG and catalytic residues predicted for lipolytic activity...
January 22, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/28125665/deregulated-lncrnas-in-b-cells-from-patients-with-active-tuberculosis
#9
Yurong Fu, Xianqin Xu, Junfang Xue, Wenping Duan, Zhengjun Yi
Role of lncRNAs in human adaptive immune response to TB infection is largely unexplored. To address this issue, here we characterized lncRNA expression profile in primary human B cell response to TB infection using microarray assay. Several lncRNAs and mRNAs were chosen for RT-qPCR validation. Bioinformatics prediction was applied to delineate function of the deregulated mRNAs. We found that 844 lncRNAs and 597 mRNAs were differentially expressed between B cell samples from individuals with or without TB. KEGG pathway analysis for the deregulated mRNAs indicated a number of pathways, such as TB, TLR signaling pathway and antigen processing and presentation...
2017: PloS One
https://www.readbyqxmd.com/read/28122644/mtb-specific-lymphocyte-responses-are-impaired-in-tuberculosis-patients-with-pulmonary-cavities
#10
Jun Wang, Yaping Dai, Jun Liu, Yongmei Yin, Hao Pei
OBJECTIVE: Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis (MTB), is a global health problem. Because the failing immune response in the lung can lead to formation of a pulmonary cavity, this study was designed to clarify MTB-specific lymphocyte responses in TB patients with pulmonary cavities. METHODS: We utilized culture filtrate protein 10 (CFP-10) and early secretory antigenic target 6 (ESAT-6) as immunogenic MTB antigens following overnight stimulation of peripheral blood mononuclear cells (PBMCs)...
January 26, 2017: European Journal of Medical Research
https://www.readbyqxmd.com/read/28118407/effect-of-physical-exercise-on-the-febrigenic-signaling-is-modulated-by-preoptic-hydrogen-sulfide-production
#11
Jonatas E Nogueira, Renato N Soriano, Rodrigo A R Fernandez, Heloísa D C Francescato, Rafael S Saia, Terezila M Coimbra, José Antunes-Rodrigues, Luiz G S Branco
We tested the hypothesis that the neuromodulator hydrogen sulfide (H2S) in the preoptic area (POA) of the hypothalamus modulates the febrigenic signaling differently in sedentary and trained rats. Besides H2S production rate and protein expressions of H2S-related synthases cystathionine β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MPST) and cystathionine γ-lyase (CSE) in the POA, we also measured deep body temperature (Tb), circulating plasma levels of cytokines and corticosterone in an animal model of systemic inflammation...
2017: PloS One
https://www.readbyqxmd.com/read/28076390/il-37-confers-protection-against-mycobacterial-infection-involving-suppressing-inflammation-and-modulating-t-cell-activation
#12
Haipeng Liu, Ruijuan Zheng, Peng Wang, Hua Yang, Xin He, Qun Ji, Wenjuan Bai, Hao Chen, Jianxia Chen, Wenxia Peng, Siyu Liu, Zhonghua Liu, Baoxue Ge
Interleukin-37 (IL-37), a novel member of the IL-1 family, plays fundamental immunosuppressive roles by broadly reducing both innate inflammation and acquired immunity, but whether it is involved in the pathogenesis of tuberculosis (TB) has not been clearly elucidated. In this study, single nucleotide polymorphism (SNP) analysis demonstrated an association of the genetic variant rs3811047 of IL-37 with TB susceptibility. In line with previous report, a significant elevated IL-37 abundance in the sera and increased expression of IL-37 protein in the peripheral blood mononuclear cells (PBMC) were observed in TB patients in comparison to healthy controls...
2017: PloS One
https://www.readbyqxmd.com/read/28068297/fatty-acid-derivative-chemokine-and-cytokine-profiles-in-exhaled-breath-condensates-can-differentiate-adult-and-children-paucibacillary-tuberculosis-patients
#13
Sergio Fabián Mosquera-Restrepo, Ana Cecilia Caro, Luis F García, Carlos Alberto Peláez-Jaramillo, Mauricio Rojas
The anti-mycobacterial immune response in adults and children with tuberculosis (TB), as well as the response in bacteriologically positive and negative patients, is different. However, knowledge of the immunological events occurring in the lungs in these clinical situations remains scarce. Exhaled breath condensate (EBC) samples may be useful for studying the inflammatory environment of the lower airways in TB patients. The fatty acid, cytokine, and chemokine profiles in EBC from healthy adults; smear-positive and smear-negative adult patients; and healthy, asthmatic, and TB children were determined using gas chromatography and LUMINEX, respectively...
January 9, 2017: Journal of Breath Research
https://www.readbyqxmd.com/read/28061954/multiple-cytokine-responses-in-discriminating-between-active-tuberculosis-and-latent-tuberculosis-infection
#14
Jing Wu, Sen Wang, Chanyi Lu, Lingyun Shao, Yan Gao, Zumo Zhou, Heqing Huang, Ying Zhang, Wenhong Zhang
BACKGROUND: Cytokines play an important role in cell-mediated immune responses against Mycobacterium tuberculosis (Mtb) infection. Cytokine profile specifically associated with active tuberculosis (ATB) patients, subjects with latent tuberculosis infection (LTBI) and non-infected individuals remains to be determined. METHODS: We enrolled a total of 92 subjects including patients with ATB (n = 25), LTBI (n = 36) and healthy controls (HC, n = 31) to investigate the cytokine production by peripheral blood mononuclear cells after Mtb purified protein derivative (PPD) stimulation which was evaluated by a beads-based multiplex assay system...
January 2017: Tuberculosis
https://www.readbyqxmd.com/read/28061952/anti-mycobacterial-function-of-macrophages-is-impaired-in-a-diet-induced-model-of-type-2-diabetes
#15
Md Abdul Alim, Suchandan Sikder, Tahnee L Bridson, Catherine M Rush, Brenda L Govan, Natkunam Ketheesan
Type 2 diabetes (T2D) is one of the major risk factors for tuberculosis (TB). In this study, a diet induced murine model of T2D (DIMT2D) was developed and characterized in the context of metabolic, biochemical and histopathological features following diet intervention. Mycobacterial susceptibility was investigated using Mycobacterium fortuitum as a surrogate. Phagocytic capability of alveolar macrophages and resident peritoneal macrophages were determined by in vitro assays using mycolic acid coated beads and M...
January 2017: Tuberculosis
https://www.readbyqxmd.com/read/28061947/b-lymphocytes-forming-follicle-like-structures-in-the-lung-tissue-of-tuberculosis-infected-mice-dynamics-phenotypes-and-functional-activity
#16
Irina Linge, Alexander Dyatlov, Elena Kondratieva, Vadim Avdienko, Alexander Apt, Tatiana Kondratieva
During tuberculosis (TB) infection, B cells form follicles in close vicinity of lung granuloma. We assessed the dynamics of follicle formation, surface phenotypes and functional activity of lung B cells during TB course in genetically susceptible mice. The follicles appeared early post infection and peaked at weeks 7-8. Lung B cells resembled classical B2 cells (CD19(+)IgMloIgD(hi)CD1d(-)CD21/35(int)CD5(-)CD11b(-)CD43(-)), but differed from them by the absence of B2 marker CD23. Lung B-cells constitutively expressed MHC II molecules, presented mycobacterial antigens to immune CD4(+) T-cells and produced high amounts of IL-6 and IL-11, but no classical type 1 (TNF-α, IFN-γ), or anti-inflammatory (IL-10, TGF-β) cytokines...
January 2017: Tuberculosis
https://www.readbyqxmd.com/read/28060545/safety-and-immunogenicity-of-adenovirus-35-tb-vaccine-candidate-in-adults-with-active-or-previous-tb-a-randomized-trial
#17
Richard N van Zyl-Smit, Aliasgar Esmail, Mary E Bateman, Rodney Dawson, Jonathan Goldin, Eva van Rikxoort, Macaya Douoguih, Maria Grazia Pau, Jerald C Sadoff, J Bruce McClain, Margaret Ann Snowden, Jacqueline Benko, David A Hokey, Kathryn Tucker Rutkowski, Andrew Graves, Barbara Shepherd, Sadritdin Ishmukhamedov, Benjamin M N Kagina, Brian Abel, Willem A Hanekom, Thomas J Scriba, Eric D Bateman
RATIONALE: Administration of tuberculosis vaccines in participants with previous or current pulmonary tuberculosis may have the potential for causing harmful post-vaccination immunological (Koch-type) reactions. OBJECTIVES: To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored tuberculosis candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary tuberculosis...
January 6, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28057604/biological-markers-in-the-diagnosis-of-tuberculous-pleural-effusion
#18
Bastien Mollo, Stéphane Jouveshomme, François Philippart, Benoît Pilmis
Tuberculosis is one of the main etiologies to evoke in the context of lymphocyte pleurisy. However, diagnosis is difficult and is based on mycobacteriology that is not enough sensitive and time-consuming, or on histology that requires invasive biopsy gesture. This literature review, carried out from Medline, summarizes the main meta-analyzes, reviews, and originator publications in English on biomarkers, classic and more innovative, studied for the diagnosis of tuberculous pleurisy. Among the immuno-biochemical markers, interferon-γ (IFN-γ), isoenzyme of adenosine deaminase 2 (ADA2) and total adenosine deaminase (ADA) seem the most relevant with respective sensitivities of 89% (87-91), 97...
February 1, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/28043864/a-simple-and-highly-effective-catalytic-nanozyme-scavenger-for-organophosphorus-neurotoxins
#19
Elena N Efremenko, Ilya V Lyagin, Natalia L Klyachko, Tatiana Bronich, Natalia V Zavyalova, Yuhang Jiang, Alexander V Kabanov
A simple and highly efficient catalytic scavenger of poisonous organophosphorus compounds, based on organophosphorus hydrolase (OPH, EC 3.1.8.1), is produced in aqueous solution by electrostatic coupling of the hexahistidine tagged OPH (His6-OPH) and poly(ethylene glycol)-b-poly(l-glutamic acid) diblock copolymer. The resulting polyion complex, termed nano-OPH, has a spherical morphology and a diameter from 25nm to 100nm. Incorporation of His6-OPH in nano-OPH preserves catalytic activity and increases stability of the enzyme allowing its storage in aqueous solution for over a year...
December 31, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28043584/increased-mycobacterium-tuberculosis-antigen-induced-gene-expression-of-interferon-gamma-tumor-necrosis-factor-alpha-and-interleukin-6-in-patients-with-diabetes
#20
Kiran I Masood, Muhammad Irfan, Qamar Masood, Bushra Jamil, Shoaib Rao, Maryam Rahim, Zahra Hasan
INTRODUCTION: Pakistan ranks fifth in high tuberculosis (TB)-burden countries and seventh among countries with high prevalence rates of diabetes mellitus (DM). DM is a risk factor for TB and worsens disease outcomes. Furthermore, Mycobacterium tuberculosis (MTB) infection can induce glucose intolerance and worsen glycemic control in diabetes. Suppressor of cytokine signaling (SOCS)-1 and -3 molecules regulate cytokine signaling and are important in maintaining an immune balance. In TB, interleukin (IL)-6 upregulation induces SOCS3, which is also a negative regulator of insulin signaling...
December 2016: International Journal of Mycobacteriology
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