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https://www.readbyqxmd.com/read/28928738/age-stratified-t-cell-responses-in-children-infected-with-mycobacterium-tuberculosis
#1
Alexandra Dreesman, Véronique Corbière, Violette Dirix, Kaat Smits, Sara Debulpaep, Iris De Schutter, Myriam Libin, Mahavir Singh, Anne Malfroot, Camille Locht, Françoise Mascart
Tuberculosis (TB) in young children differs from adult TB in that the risk of rapid progression to active TB (aTB) is higher in children than in adults. The reasons for this increased risk are not fully understood. Early differentiation remains difficult between children at risk to develop aTB from those who will remain healthy and develop a latent TB infection (LTBI). Biomarkers to differentiate aTB from LTBI in children, especially in very young children, are urgently needed. To identify M. tuberculosis-specific functional T cell subsets related to clinical manifestations in children, we enrolled 87 children exposed to M...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28888638/the-response-of-red-deer-to-oral-administration-of-heat-inactivated-mycobacterium-bovis-and-challenge-with-a-field-strain
#2
Jobin Thomas, María Ángeles Risalde, Miriam Serrano, Iker Sevilla, Mariví Geijo, José Antonio Ortíz, Miguel Fuertes, José Francisco Ruíz-Fons, José de la Fuente, Lucas Domínguez, Ramón Juste, Joseba Garrido, Christian Gortázar
Deer species (family Cervidae) are often part of the Mycobacterium tuberculosis complex maintenance host community, and tuberculosis (TB) control in deer, including vaccination, is consequently an area of ongoing research. However, most research into deer vaccination against TB is focused on using the live bacillus Calmette Guerin (BCG). Oral inactivated vaccines represent an interesting alternative to either oral or parenteral BCG, since neither diagnostic cross-reactions nor vaccine strain survival are likely to occur...
September 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28877927/protective-vaccine-efficacy-of-the-complete-form-of-ppe39-protein-from-mycobacterium-tuberculosis-beijing-k-strain-in-mice
#3
Ahreum Kim, Yun-Gyoung Hur, Sunwha Gu, Sang-Nae Cho
The aim of this study was to evaluate the protective efficacy of MTBK_24820, a complete form of PPE39 protein derived from a predominant Beijing/K strain of Mycobacterium tuberculosis in South Korea. Mice were immunized with MTKB_24820, M. bovis Bacilli Calmette-Guérin, or adjuvant prior to a high-dosed Beijing/K strain aerosol infection. After 4 and 9 weeks, bacterial loads were determined and histopathologic and immunologic features in the lungs and spleens of the M. tb-infected mice were analyzed. Putative immunogenic T-cell epitopes were examined using synthetic overlapping peptides...
September 6, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28871253/severe-tuberculosis-in-humans-correlates-best-with-neutrophil-abundance-and-lymphocyte-deficiency-and-does-not-correlate-with-antigen-specific-cd4-t-cell-response
#4
Alexander V Panteleev, Irina Yu Nikitina, Irina A Burmistrova, George A Kosmiadi, Tatyana V Radaeva, Rasul B Amansahedov, Pavel V Sadikov, Yana V Serdyuk, Elena E Larionova, Tatef R Bagdasarian, Larisa N Chernousova, Vitaly V Ganusov, Irina V Lyadova
It is generally thought that Mycobacterium tuberculosis (Mtb)-specific CD4(+) Th1 cells producing IFN-γ are essential for protection against tuberculosis (TB). In some studies, protection has recently been associated with polyfunctional subpopulation of Mtb-specific Th1 cells, i.e., with cells able to simultaneously secrete several type 1 cytokines. However, the role for Mtb-specific Th1 cells and their polyfunctional subpopulations during established TB disease is not fully defined. Pulmonary TB is characterized by a great variability of disease manifestations...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28854691/the-clinical-recovery-of-tuberculosis-patients-undergoing-specific-treatment-is-associated-with-changes-in-the-immune-and-neuroendocrine-responses
#5
Ariana Díaz, Bettina Bongiovanni, Luciano D'Attilio, Natalia Santucci, Griselda Dídoli, Rocío Del Valle Fernández, Leandro Kovalevski, Susana Lioi, Walter Gardeñez, Nadia Brandan, Luis J Nannini, Hugo Besedovsky, Adriana Del Rey, Oscar Bottasso, María Luisa Bay
Tuberculosis (TB) caused by Mycobacterium tuberculosis is a health problem worldwide. Patients with pulmonary TB show a neuro-immune-endocrine imbalance characterized by an impaired cellular immunity together with increased plasma levels of cortisol, pro- and anti-inflammatory cytokines and markedly decreased dehydroepiandrosterone (DHEA) levels. Extending these findings, we now investigated the immune-endocrine profile of TB patients undergoing specific treatment. Patients (n = 24) were bled at diagnosis (T0), 2, 4, 6 months after treatment initiation and 3 months following its completion...
September 29, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28837654/immune-characterization-of-the-hbha-specific-response-in-mycobacterium-tuberculosis-infected-patients-with-or-without-hiv-infection
#6
Teresa Chiacchio, Giovanni Delogu, Valentina Vanini, Gilda Cuzzi, Flavio De Maio, Carmela Pinnetti, Alessandro Sampaolesi, Andrea Antinori, Delia Goletti
INTRODUCTION: RD1-based Interferon-γ Release Assays (IGRAs) cannot distinguish latent from active tuberculosis (TB) disease. Conversely, a positive response to heparin-binding haemagglutinin (HBHA)-based IGRAs, among TB-infected subjects, correlates with Mycobacterium tuberculosis (Mtb) containment and low risk of TB progression. The aim of this study was to characterize HBHA-immune responses in HIV-infected and uninfected subjects with active TB or latent TB infection (LTBI). METHODS: 49 subjects were prospectively enrolled: 22 HIV-uninfected (13 TB, 9 LTBI) and 27 HIV-infected (12 HIV-TB, 15 HIV-LTBI)...
2017: PloS One
https://www.readbyqxmd.com/read/28832027/protein-kinase-c-delta-pkc%C3%AE-a-marker-of-inflammation-and-tuberculosis-disease-progression-in-humans-is-important-for-optimal-macrophage-killing-effector-functions-and-survival-in-mice
#7
S P Parihar, M Ozturk, M J Marakalala, D T Loots, R Hurdayal, D Beukes, M Van Reenen, D E Zak, S K Mbandi, F Darboe, A Penn-Nicholson, W A Hanekom, M Leitges, T J Scriba, R Guler, F Brombacher
We previously demonstrated that protein kinase C-δ (PKCδ) is critical for immunity against Listeria monocytogenes, Leishmania major, and Candida albicans infection in mice. However, the functional relevance of PKCδ during Mycobacterium tuberculosis (Mtb) infection is unknown. PKCδ was significantly upregulated in whole blood of patients with active tuberculosis (TB) disease. Lung proteomics further revealed that PKCδ was highly abundant in the necrotic and cavitory regions of TB granulomas in multidrug-resistant human participants...
August 23, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28802400/mycobacterium-tuberculosis-myma-is-a-tlr2-agonist-that-activate-macrophages-and-a-th1-response
#8
Iti Saraav, Swati Singh, Kirti Pandey, Monika Sharma, Sadhna Sharma
Cell wall of Mycobacterium tuberculosis (M.tb) is a major source of immunogenic proteins that can be tested as vaccine candidates. MymA (Rv3083), a 55 kDa M.tb flavin containing monooxygenase, is involved in modification of mycolic acids during acidic shock following M.tb internalization in macrophage. In this study, we have investigated the role of this cell wall associated protein in activation of macrophages by toll like receptor (TLRs) engagement and subsequent signaling. Our results showed that MymA stimulation of THP1 cells and human monocyte derived macrophages (MDM) lead to upregulation of TLR2 and co-stimulatory molecules CD40, CD80, CD86 and HLA-DR...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28783414/guanine-nucleotide-exchange-factor-h1-promotes-inflammatory-cytokine-production-and-intracellular-mycobacterial-elimination-in-macrophages
#9
Hui Wang, Jinli Wang, Jiahui Yang, Xiaofan Yang, Jianchun He, Ruining Wang, Sudong Liu, Lin Zhou, Li Ma
Mycobacterium tuberculosis (M.tb), which causes tuberculosis, is a host-adapted intracellular pathogen that can live within macrophages owning to its ability to arrest phagolysosome biogenesis. The guanine nucleotide exchange factor H1 (GEF-H1) may contribute to the phagocytosis of bacteria by macrophages through mediating the crosstalk between microtubules and the actin cytoskeleton. Its role in Shigella infection has been determined but little is known about the role of GEF-H1 in mycobacterial infection. In the present study, we demonstrated that GEF-H1 functioned as a key regulator of the macrophage-mediated anti-mycobacterial response...
September 17, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28767735/engaging-the-cd40-cd40l-pathway-augments-t-helper-cell-responses-and-improves-control-of-mycobacterium-tuberculosis-infection
#10
Jonathan Kevin Sia, Erica Bizzell, Ranjna Madan-Lala, Jyothi Rengarajan
Mycobacterium tuberculosis (Mtb) impairs dendritic cell (DC) functions and induces suboptimal antigen-specific CD4 T cell immune responses that are poorly protective. Mucosal T-helper cells producing IFN-γ (Th1) and IL-17 (Th17) are important for protecting against tuberculosis (TB), but the mechanisms by which DCs generate antigen-specific T-helper responses during Mtb infection are not well defined. We previously reported that Mtb impairs CD40 expression on DCs and restricts Th1 and Th17 responses. We now demonstrate that CD40-dependent costimulation is required to generate IL-17 responses to Mtb...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28759590/mixed-th1-and-th2-mycobacterium-tuberculosis-specific-cd4-t-cell-responses-in-patients-with-active-pulmonary-tuberculosis-from-tanzania
#11
Patrizia Amelio, Damien Portevin, Klaus Reither, Francis Mhimbira, Maxmillian Mpina, Anneth Tumbo, Beatrice Nickel, Hanspeter Marti, Stefanie Knopp, Song Ding, Adam Penn-Nicholson, Fatoumatta Darboe, Khalid Ohmiti, Thomas J Scriba, Giuseppe Pantaleo, Claudia Daubenberger, Matthieu Perreau
Mycobacterium tuberculosis (Mtb) and helminth infections elicit antagonistic immune effector functions and are co-endemic in several regions of the world. We therefore hypothesized that helminth infection may influence Mtb-specific T-cell immune responses. We evaluated the cytokine profile of Mtb-specific T cells in 72 individuals with pulmonary TB disease recruited from two Sub-Saharan regions with high and moderate helminth burden i.e. 55 from Tanzania (TZ) and 17 from South Africa (SA), respectively. We showed that Mtb-specific CD4 T-cell functional profile of TB patients from Tanzania are primarily composed of polyfunctional Th1 and Th2 cells, associated with increased expression of Gata-3 and reduced expression of T-bet in memory CD4 T cells...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28759253/differential-recognition-of-mtb-specific-epitopes-as-a-function-of-tuberculosis-disease-history
#12
Thomas J Scriba, Chelsea Carpenter, Sebastian Carrasco Pro, John Sidney, Munyaradzi Musvosvi, Virginie Rozot, Grégory Seumois, Sandy L Rosales, Pandurangan Vijayanand, Delia Goletti, Edward Makgotlho, Willem Hanekom, Mark Hatherill, Bjoern Peters, Alessandro Sette, Cecilia S Lindestam Arlehamn
RATIONALE: Individuals with a history of tuberculosis disease are at elevated risk of disease recurrance. The underlying cause is not known, but one explanation is that previous disease results in less effective immunity against Mycobacterium tuberculosis (Mtb). OBJECTIVE: We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection (LTBI) differs as a function of previous diagnosis of active tuberculosis (TB) disease...
July 31, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28744263/recombinant-invasive-lactococcus-lactis-carrying-a-dna-vaccine-coding-the-ag85a-antigen-increases-inf-%C3%AE-il-6-and-tnf-%C3%AE-cytokines-after-intranasal-immunization
#13
Pamela Mancha-Agresti, Camila Prosperi de Castro, Janete S C Dos Santos, Maíra A Araujo, Vanessa B Pereira, Jean G LeBlanc, Sophie Y Leclercq, Vasco Azevedo
Tuberculosis (TB) remains a major threat throughout the world and in 2015 it caused the death of 1.4 million people. The Bacillus Calmette-Guérin is the only existing vaccine against this ancient disease; however, it does not provide complete protection in adults. New vaccines against TB are eminently a global priority. The use of bacteria as vehicles for delivery of vaccine plasmids is a promising vaccination strategy. In this study, we evaluated the use of, an engineered invasive Lactococcus lactis (expressing Fibronectin-Binding Protein A from Staphylococcus aureus) for the delivery of DNA plasmid to host cells, especially to the mucosal site as a new DNA vaccine against tuberculosis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28741242/the-weakening-effect-of-soluble-epoxide-hydrolase-inhibitor-auda-on-febrile-response-to-lipopolysaccharide-and-turpentine-in-rat
#14
Jakub Piotrowski, Tomasz Jędrzejewski, Małgorzata Pawlikowska, Agata Joanna Pacuła, Jacek Ścianowski, Wiesław Kozak
A still growing body of evidence suggests the importance of epoxyeicosatrienoic acids (EETs) in the regulation of inflammatory response; therefore, drugs that stabilize their levels by targeting the soluble epoxide hydrolase (sEH), an enzyme responsible for their metabolism, are currently under investigation. The effect of sEH inhibitors on molecular components of fever mechanism, i.e., on synthesis of pro-inflammatory cytokines or prostaglandins, has been repeatedly proven; however, the hypothesis that sEH inhibitors affect febrile response has never been tested...
July 24, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28735813/atypical-memory-b-cells-in-human-chronic-infectious-diseases-an-interim-report
#15
Silvia Portugal, Nyamekye Obeng-Adjei, Susan Moir, Peter D Crompton, Susan K Pierce
Immunological memory is a remarkable phenomenon in which survival of an initial infection by a pathogen leads to life-long protection from disease upon subsequent exposure to that same pathogen. For many infectious diseases, long-lived protective humoral immunity is induced after only a single infection in a process that depends on the generation of memory B cells (MBCs) and long-lived plasma cells. However, over the past decade it has become increasingly evident that many chronic human infectious diseases to which immunity is not readily established, including HIV-AIDS, malaria and TB, are associated with fundamental alterations in the composition and functionality of MBC compartments...
July 11, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28728855/tissue-plasminogen-activator-tpa-signal-sequence-enhances-immunogenicity-of-mva-based-vaccine-against-tuberculosis
#16
Yiming Kou, Yongqing Xu, Zhilei Zhao, Jie Liu, Yang Wu, Qingrui You, Linli Wang, Feng Gao, Linjun Cai, Chunlai Jiang
Tuberculosis (TB) remains a serious health problem worldwide, and the only available vaccine, bacillus Calmette-Guérin (BCG), has shown highly variable efficacy in adults against TB. New vaccines are urgently needed, and the modified vaccinia virus Ankara (MVA)-based vaccine has emerged as one of the most promising candidates based on many preclinical and early clinical studies over the past few years. However, the maximum tolerable dose and strength of induced immune responses have limited the protective effect of MVA-based prophylactic vaccines...
July 17, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28713838/role-of-interferons-in-the-development-of-diagnostics-vaccines-and-therapy-for-tuberculosis
#17
REVIEW
Kai Ling Chin, Fadhilah Zulkipli Anis, Maria E Sarmiento, Mohd Nor Norazmi, Armando Acosta
Tuberculosis (TB) is an airborne infection caused by Mycobacterium tuberculosis (Mtb). About one-third of the world's population is latently infected with TB and 5-15% of them will develop active TB in their lifetime. It is estimated that each case of active TB may cause 10-20 new infections. Host immune response to Mtb is influenced by interferon- (IFN-) signaling pathways, particularly by type I and type II interferons (IFNs). The latter that consists of IFN-γ has been associated with the promotion of Th1 immune response which is associated with protection against TB...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28709490/serum-levels-of-soluble-urokinase-plasminogen-activator-receptor-supar-as-a-marker-of-tuberculosis-treatment-efficacy
#18
V Indumati, V Vijay, D Krishnaswamy, V Rajeshwari, A Ramesh, D Shantala, A Shilpa
BACKGROUND: Upon diagnosis, Pulmonary Tuberculosis patients are treated for TB for a period of 6-9 months. At present, there exists very little indication of the efficacy of the particular treatment. A few previous studies have shown that soluble urokinase plasminogen activator receptor (SuPAR) may be used as treatment efficacy marker. SuPAR is a cellular receptor for serine protease urokinase plasminogen activator (uPA). Bacterial endotoxins and cytokines of the innate immune system stimulate the secretion of uPA in monocytes & neutrophils...
July 2017: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/28694808/mycobacterium-tuberculosis-dosr-regulon-gene-rv2004c-encodes-a-novel-antigen-with-pro-inflammatory-functions-and-potential-diagnostic-application-for-detection-of-latent-tuberculosis
#19
Sankara Narayana Doddam, Vidyullatha Peddireddy, Niyaz Ahmed
Approximately 1.7 billion people in the world harbor latent Mycobacterium tuberculosis (Mtb) with a substantial risk of progression to clinical outcome. Containment of these seed beds of Mtb is essential to eliminate tuberculosis completely in high burden settings such as India. Hence, there is an urgent need for the identification of new serological markers for detection or vaccine candidates to prevent latent tuberculosis infection (LTBI). DosR regulon antigens of Mtb might serve as attractive targets for LTBI diagnosis or vaccine development as they are specifically expressed and are upregulated during latent phase...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28683527/host-directed-therapeutics-as-novel-angle-for-tuberculosis-treatment
#20
REVIEW
Ye-Ram Kim, Chul-Su Yang
Despite significant efforts to improve tuberculosis (TB) treatment, it remains a worldwide infectious disease due to the limitations of current TB regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors is beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs are more beneficial than existed TB drugs, which are limited the long durations of treatment and the emergence of drug-resistant strains...
July 7, 2017: Journal of Microbiology and Biotechnology
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