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Tuberculosis and immune response

Kirstin Harling, Ernest Adankwah, Alptekin Güler, Anthony Afum-Adjei Awuah, Louis Adu-Amoah, Ertan Mayatepek, Ellis Owusu-Dabo, Norman Nausch, Marc Jacobsen
T-cells critically contribute to protection against Mycobacterium tuberculosis infection, and impaired T-cell responses can lead to disease progression. Pro-inflammatory and immunosuppressive cytokines affect T-cells, and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell function. Constitutive STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune diseases...
March 19, 2018: Cellular & Molecular Immunology
Jale Moradi, Maryam Izad, Mina Tabrizi, Nader Mosavari, Behnaz Esmaeili, Mohammad Mehdi Feizabadi
One third of the world population are latently infected with Mycobacterium tuberculosis and are at the risk of reactivation of tuberculosis (TB). The most effective strategy for control of TB worldwide is the development of a vaccine that inhibits progression of latent TB to active infection. In this study, two optimized constructs consisting of multi-epitopes DNA derived from three latency antigens Rv2029c, Rv2031c, and Rv2627c fused with or without light chain 3 (LC3) are synthetized. The immunogenicity effectiveness of two DNA constructs was evaluated in the mouse model...
March 19, 2018: Acta Microbiologica et Immunologica Hungarica
Cristian Alfredo Segura-Cerda, Michel de Jesús Aceves-Sánchez, Brenda Marquina-Castillo, Dulce Mata-Espinoza, Jorge Barrios-Payán, Perla Jazmín Vega-Domínguez, César Pedroza-Roldán, Jorge Bravo-Madrigal, Alba Adriana Vallejo-Cardona, Rogelio Hernández-Pando, Mario Alberto Flores-Valdez
Pellicles, a type of biofilm, have gathered a renewed interest in the field of tuberculosis as a structure that mimics some characteristics occurring during M. tuberculosis infection, such as antibiotic recalcitrance and chronicity of infection, and as a source of antigens for humoral response in infected guinea pigs. In other bacteria, it has been well documented that the second messenger c-di-GMP modulates the transition from planktonic cells to biofilm formation. In this work, we used the live vaccine Mycobacterium bovis BCG to determine whether deletion of genes involved in c-di-GMP metabolism would affect interaction with macrophages, capacity to induce immune response in a murine cell line and mice, and how the protein profile was modified when grown as surface pellicles...
March 14, 2018: Vaccine
Joel D Ernst, Amber Cornelius, Ludovic Desvignes, Jacqueline Tavs, Brian A Norris
Infection with M. tuberculosis is associated with inconsistent and incomplete elimination of the bacteria, despite development of antigen-specific T cell responses. One mechanism employed by M. tuberculosis is to limit availability of antigen for activation of CD4 T cells. We examined the utility of systemic administration of epitope peptides to activate pre-existing T cells in mice infected with M. tuberculosis. We found that systemic peptide administration: 1) selectively activates T cells specific for the epitope peptide; 2) loads MHC class II on lung macrophages and dendritic cells; 3) activates CD4 T cells in the lung parenchyma; 4) has little antimycobacterial activity...
March 14, 2018: Journal of Infectious Diseases
Mario Alberto Flores-Valdez, Cristian Alfredo Segura-Cerda, Jorge Gaona-Bernal
Effective prevention of tuberculosis (Tb) would undoubtedly be of paramount relevance in the control of its global burden, which resulted in more than 6 million new cases in 2016. Research aimed to improve the current vaccine, Bacillus Calmette- Guérin (BCG), or directed to develop new candidates, has taken into account the interaction between the host and Mycobacterium tuberculosis (Mtb). Recently, autophagy, an intracellular process of the host, has been shown to act as a mechanism that contributes to bacilli clearance in vitro and in vivo...
March 13, 2018: Molecular Immunology
Cheleka A M Mpande, One B Dintwe, Munyaradzi Musvosvi, Simbarashe Mabwe, Nicole Bilek, Mark Hatherill, Elisa Nemes, Thomas J Scriba
Background: Maintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM ), which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM ) or effector (TEFF ) T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM . We aimed to determine if infection with Mycobacterium tuberculosis ( M. tb ), the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology...
2018: Frontiers in Immunology
Nomakorinte Gcebe, Victor P M G Rutten, Nicolaas Gey van Pittius, Brendon Naicker, Anita L Michel
Some species of non-tuberculous mycobacteria (NTM) have been reported to be opportunistic pathogens of animals and humans. Recently there has been an upsurge in the number of cases of NTM infections, such that some NTM species are now recognized as pathogens of humans and animals. From a veterinary point of view, the major significance of NTM is the cross-reactive immune response they elicit against Mycobacterium bovis antigens, leading to misdiagnosis of bovine tuberculosis. Four NTM isolates were detected from a bovine nasal swab, soil and water, during an NTM survey in South Africa...
March 15, 2018: International Journal of Systematic and Evolutionary Microbiology
Wendy E Whatney, Neel R Gandhi, Cecilia S Lindestam Arlehamn, Azhar Nizam, Hao Wu, Melanie J Quezada, Angela Campbell, Salim Allana, Mbuyi Madeleine Kabongo, Jeremiah Khayumbi, Benson Muchiri, Joshua Ongalo, Joan Tonui, Loren E Sasser, Tawania J Fergus, Gregory Sadat Ouma, Samuel Gurrion Ouma, Allison A Beck, Mark J Mulligan, Alawode Oladele, Deepak Kaushal, Kevin P Cain, Lance Waller, Henry M Blumberg, John D Altman, Joel D Ernst, Jyothi Rengarajan, Cheryl L Day
Antigen-specific CD4 and CD8 T cells are important components of the immune response to Mycobacterium tuberculosis , yet little information is currently known regarding how the breadth, specificity, phenotype, and function of M. tuberculosis -specific T cells correlate with M. tuberculosis infection outcome in humans. To facilitate evaluation of human M. tuberculosis -specific T cell responses targeting multiple different Ags, we sought to develop a high throughput and reproducible T cell response spectrum assay requiring low blood sample volumes...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Wenting He, Shengfeng Hu, Xialin Du, Qian Wen, Xiao-Ping Zhong, Xinying Zhou, Chaoying Zhou, Wenjing Xiong, Yuchi Gao, Shimeng Zhang, Ruining Wang, Jiahui Yang, Li Ma
The mechanisms by which vitamins regulate immunity and their effect as an adjuvant treatment for tuberculosis have gradually become very important research topics. Studies have found that vitamin B5 (VB5) can promote epithelial cells to express inflammatory cytokines. We aimed to examine the proinflammatory and antibacterial effect of VB5 in macrophages infected with Mycobacterium tuberculosis (MTB) strain H37Rv and the therapeutic potential of VB5 in vivo with tuberculosis. We investigated the activation of inflammatory signal molecules (NF-κB, AKT, JNK, ERK, and p38), the expression of two primary inflammatory cytokines (tumor necrosis factor and interleukin-6) and the bacterial burdens in H37Rv-infected macrophages stimulated with VB5 to explore the effect of VB5 on the inflammatory and antibacterial responses of macrophages...
2018: Frontiers in Immunology
Maopeng Tian, Zijie Zhou, Songwei Tan, Xionglin Fan, Longmeng Li, Nadeem Ullah
Despite the vaccine Mycobacterium bovis Bacillus Calmette-Guérin is used worldwide, tuberculosis (TB) remains the first killer among infectious diseases. An effective vaccine is urgently required. DNA vaccine has shown prophylactic as well as therapeutic effects against TB, while its weak immunogenicity hinders the application. As a strong inducer of Th1-biased immune response, DMT, consisting of dimethyldioctadecylammonium (DDA) and two pattern recognition receptor agonists monophosphoryl lipid A and trehalose 6,6'-dibehenate (TDB), was a newly developed liposomal adjuvant...
2018: Frontiers in Immunology
Cong Chen, Tao Yan, Liguo Liu, Jianmin Wang, Qi Jin
Tuberculosis (TB) is a major comorbidity in HIV patients as well as a serious co-epidemic. Traditional detection methods are not effective or sensitive for the detection of Mycobacterium tuberculosis at the early stage. TB has become a major cause of lethal on HIV patients. We employed isobaric tags for relative and absolute quantitation (iTRAQ) technology to identify the different host responses in HIV-noTB and HIV-TB patients' sera. Given the diversity of HIV subtypes, which results in a variety of host responses in different human populations, we focused on the Chinese patients...
2018: Frontiers in Microbiology
Xiang Zhang, Adil Mardinoglu, Leo A B Joosten, Jan A Kuivenhoven, Yang Li, Mihai G Netea, Albert K Groen
Immunity and cellular metabolism are tightly interconnected but it is not clear whether different pathogens elicit specific metabolic responses. To address this issue, we studied differential metabolic regulation in peripheral blood mononuclear cells (PBMCs) of healthy volunteers challenged by Candida albicans, Borrelia burgdorferi , lipopolysaccharide, and Mycobacterium tuberculosis in vitro . By integrating gene expression data of stimulated PBMCs of healthy individuals with the KEGG pathways, we identified both common and pathogen-specific regulated pathways depending on the time of incubation...
2018: Frontiers in Physiology
Yu Wang, Miao-Miao Zhang, Wei-Wei Huang, Shou-Quan Wu, Ming-Gui Wang, Xiao-Yan Tang, Andrew J Sandford, Jian-Qing He
Background: The toll-like receptor 2 (TLR2)-mediated immune response is critical for host defense against Mycobacterium tuberculosis . There is evidence that TLR10, a TLR2 signaling modulator, may be involved in progression of tuberculosis (TB). Methods: Using a self-validating case-control design, we tested for an association between seven TLR10 polymorphisms and susceptibility to TB in three independent series with two distinct populations. Single-nucleotide polymorphism (SNP) genotypes were determined by the SNPscanTM method...
2018: Frontiers in Immunology
Leonardo Silva de Araujo, Nidai de Bárbara Moreira da Silva, Janaina Aparecida Medeiros Leung, Fernanda Carvalho Queiroz Mello, Maria Helena Féres Saad
Despite the reported high heterogeneity of the human immune response to tuberculosis (TB), new studies may contribute to the understanding of Mycobacterium tuberculosis immunopathogenesis. To investigate the patterns of humoral response during latent (LTBI) and active TB, we evaluated specific IgG subclasses' response, by ELISA, to a set of mycobacterial antigens (Rv2029c, Rv2031c, Rv2034, Rv2628, Rv3353c ESAT6:CFP10, and the new chimeric PstS1(285-374) :CFP10) in plasma samples from exposed uninfected controls (ExC, n = 24), LTBI (n = 61), and TB (n = 15) donors...
January 2018: Tuberculosis
Elisabetta Gerace, Francesca Mandanici, Paolo Pasquali, Maria Falduto, Maria Vitale, Vincenzo Di Marco Lo Presti, Benedetta Amato
The interferon-gamma (IFN-γ) test measures cell mediated immune response (CMI) during the early stages of tuberculosis infection. Although Bovine Tuberculosis (BT) spread in feral pigs is widely documented in literature, the effectiveness of IFN-γ in this species has been only recently reported. One of the major obstacle of this assay is that whole blood samples should be stimulated with purified protein derivative (PPD) cocktail within 8 h from the blood sampling. This study set up a defined broth culture in which lymphocytes, the cell population predominantly responsible for IFN-γ production, are maintained in a steady-state and their vitality is preserved...
January 2018: Tuberculosis
E D Pieterman, F G Liqui Lung, A Verbon, H I Bax, C W Ang, J Berkhout, G Blaauw, A Brandenburg, N D van Burgel, A Claessen, K van Dijk, M Heron, M Hooghiemstra, R Leussenkamp-Hummelink, E van Lochem, I H M van Loo, B Mulder, A Ott, O Pontesilli, A Reuwer, P Rombouts, V Saegeman, M Scholing, S Vainio, J E M de Steenwinkel
OBJECTIVES: The aim of this verification study was to compare the QuantiFERON® -TB Gold Plus (QFT-Plus) to the QuantiFERON® -TB Gold In Tube (QFT-GIT). The new QFT-Plus test contains an extra antigen tube which, according to the manufacturer additionally elicits a CD8+ T-cell response above the CD4+ T-cell response. We assessed the value of this tube in detecting recent latent tuberculosis infections. METHODS: Between May 2015 and December 2016, 1031 subjects underwent QFT-Plus and QFT-GIT test...
January 2018: Tuberculosis
Xiaolei Wang, Yanhua Wu, Jin Jiao, Qing Huang
Mycobacterium tuberculosis (MTB) infection is a significant contributor to dysregulated T cell-mediated immune response. Here we aimed to evaluate the mechanism of MTB infection in promoting interleukin-10 (IL-10) upregulation. The IL-10 levels in MTB infected THP-1 cells were evaluated with enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR). In challenged THP-1 cells, the HDAC6 and HDAC11 mRNA and protein levels were monitored at varied duration after MTB infection. Further, chromatin immunoprecipitation (ChIP) analysis was used to investigate the interaction between IL-10 expression and HDAC6 or HDAC11...
January 2018: Tuberculosis
Sally A F El-Sahrigy, Azza M O Abdel Rahman, Dalia Y Samaha, Nesrine A Mohamed, Sally M Saber, Hala A Talkhan, Ghada A Ismail, Essam M Ibraheem, Emad M Riad
INTRODUCTION: Tuberculosis (TB) remains a huge worldwide burden, despite extensive vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is inadequate to protect the human population against TB. This underscore the critical necessitate to develop an improved TB vaccine, based on a better understanding of host-pathogen interactions and immune responses during mycobacterial infection. AIM OF THE WORK: To examine whether the exogenous addition of IFN-β could improve dendritic cell (DC) response to Mycobacterium bovis (M...
March 6, 2018: Journal of Immunological Methods
Violeta D Alvarez-Jiménez, Kahiry Leyva-Paredes, Mariano García-Martínez, Luis Vázquez-Flores, Víctor Gabriel García-Paredes, Marcia Campillo-Navarro, Israel Romo-Cruz, Víctor Hugo Rosales-García, Jessica Castañeda-Casimiro, Sirenia González-Pozos, José Manuel Hernández, Carlos Wong-Baeza, Blanca Estela García-Pérez, Vianney Ortiz-Navarrete, Sergio Estrada-Parra, Jeanet Serafín-López, Isabel Wong-Baeza, Rommel Chacón-Salinas, Iris Estrada-García
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb). In the lungs, macrophages and neutrophils are the first immune cells that have contact with the infecting mycobacteria. Neutrophils are phagocytic cells that kill microorganisms through several mechanisms, which include the lytic enzymes and antimicrobial peptides that are found in their lysosomes, and the production of reactive oxygen species. Neutrophils also release extracellular vesicles (EVs) (100-1,000 nm in diameter) to the extracellular milieu; these EVs consist of a lipid bilayer surrounding a hydrophilic core and participate in intercellular communication...
2018: Frontiers in Immunology
Mathieu Garand, Martin Goodier, Olumuyiwa Owolabi, Simon Donkor, Beate Kampmann, Jayne S Sutherland
Tuberculosis (TB) is still a global health concern, especially in resource-poor countries such as The Gambia. Defining protective immunity to TB is challenging: its pathogenesis is complex and involves several cellular components of the immune system. Recent works in vaccine development suggest important roles of the innate immunity in natural protection to TB, including natural killer (NK) cells. NK cells mediate cellular cytotoxicity and cytokine signaling in response to Mycobacterium tuberculosis (Mtb). NK cells can display specific memory-type markers to previous antigen exposure; thus, bridging innate and adaptive immunity...
2018: Frontiers in Immunology
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