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Th17 tuberculosis

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https://www.readbyqxmd.com/read/30104212/adjuvant-potential-of-poly-%C3%AE-l-glutamine-from-cell-wall-of-mycobacterium-tuberculosis
#1
Rajesh Mani, Manish Gupta, Anshu Malik, Ravi Tandon, Rajendra Prasad, Rakesh Bhatnagar, Nirupama Banerjee
Novel adjuvants are in demand for improving the efficacy of human vaccines. The immunomodulatory properties of Mycobacterium tuberculosis (Mtb) cell wall components have been highlighted in the formulation of complete Freund's adjuvant (CFA). We have explored the adjuvant potential of poly-α-L-glutamine (PLG), a lesser-known constituent of pathogenic mycobacterial cell wall. Immune parameters indicated that the adjuvant potency of PLG was statistically comparable to CFA and better than alum in the context of H1 antigen (Ag85B and ESAT-6 fusion)...
August 13, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/30003413/subpopulation-structure-of-ifn%C3%AE-producing-t-lymphocytes-in-patients-with-pulmonary-tuberculosis
#2
T E Kononova, O I Urazova, V V Novitskii, I E Esimova, E G Churina
The study of subpopulation structure of IFNγ-producing T cells in patients with pulmonary tuberculosis revealed a decrease in the number of CD3+ IFNγ+ cells against the background of significantly increased IFNγ secretion in vitro irrespective of the clinical form of the disease and drug sensitivity of M. tuberculosis, most strongly expressed in case of the disseminated tuberculosis. In patients with infiltrative drug-sensitive and drug-resistant pulmonary tuberculosis, increased number of Th1/Th17 lymphocytes (CD4+ IFNγ+ IL-17A+ ) and, conversely, decreased number of blood γδT cells was detected...
July 12, 2018: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29913109/specific-t-cell-induction-using-iron-oxide-based-nanoparticles-as-subunit-vaccine-adjuvant
#3
Lázaro Moreira Marques Neto, Nicholas Zufelato, Ailton Antônio de Sousa-Júnior, Monalisa Martins Trentini, Adeliane Castro da Costa, Andris Figueiroa Bakuzis, André Kipnis, Ana Paula Junqueira-Kipnis
Metal-based nanoparticles (NPs) stimulate innate immunity; however, they have never been demonstrated to be capable of aiding the generation of specific cellular immune responses. Therefore, our objective was to evaluate whether iron oxide-based NPs have adjuvant properties in generating cellular Th1, Th17 and TCD8 (Tc1) immune responses. For this purpose, a fusion protein (CMX) composed of Mycobacterium tuberculosis antigens was used as a subunit vaccine. Citrate-coated MnFe2 O4 NPs were synthesized by co-precipitation and evaluated by transmission electron microscopy...
June 18, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29743811/the-immunoregulation-of-th17-in-host-against-intracellular-bacterial-infection
#4
REVIEW
Yonghong Li, Chaojun Wei, Hui Xu, Jing Jia, Zhenhong Wei, Rui Guo, Yanjuan Jia, Yu Wu, Yuanting Li, Xiaoming Qi, Zhenhao Li, Xiaoling Gao
T helper 17 cells (Th17) constitute a distinct subset of helper T cells with a unique transcriptional profile (STAT3, ROR γ , and ROR α ), cytokine production pattern (IL17 family), and requirement of specific cytokines for their differentiation (TGF- β , IL6, IL21, and IL23). Recent studies involving experimental animals and humans have shown that Th17/IL17 plays a crucial role in host defense against a variety of pathogens, including bacteria and viruses. The underlying mechanisms by which Th17 performs include dendritic cell (DC) regulation, neutrophil recruitment, Th1 modulation, and T regulatory cell (Treg) balance...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29739853/-mycobacterium-tuberculosis-ppe60-antigen-drives-th1-th17-responses-via-toll-like-receptor-2-dependent-maturation-of-dendritic-cells
#5
Haibo Su, Zhen Zhang, Zijian Liu, Baozhou Peng, Cong Kong, Honghai Wang, Zhi Zhang, Ying Xu
Targeting of Mycobacterium tuberculosis (MTB) PE/PPE antigens that induce type 1 helper T cell (Th1) and Th17 responses represents a crucial strategy for the development of tuberculosis (TB) vaccines. However, only a few PE/PPE antigens induce these responses. Here, we sought to determine how the cell wall-associated antigen PPE60 (Rv3478) activates dendritic cell (DC) maturation and T-cell differentiation. We observed that PPE60 induces DC maturation by augmenting the protein expression of cluster of differentiation 80 (CD80) and CD86 and major histocompatibility complex (MHC) class I and MHC class II on the cell surface...
June 29, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29719256/sting-activating-adjuvants-elicit-a-th17-immune-response-and-protect-against-mycobacterium-tuberculosis-infection
#6
Erik Van Dis, Kimberly M Sogi, Chris S Rae, Kelsey E Sivick, Natalie H Surh, Meredith L Leong, David B Kanne, Ken Metchette, Justin J Leong, Jacob R Bruml, Vivian Chen, Kartoosh Heydari, Nathalie Cadieux, Tom Evans, Sarah M McWhirter, Thomas W Dubensky, Daniel A Portnoy, Sarah A Stanley
There are a limited number of adjuvants that elicit effective cell-based immunity required for protection against intracellular bacterial pathogens. Here, we report that STING-activating cyclic dinucleotides (CDNs) formulated in a protein subunit vaccine elicit long-lasting protective immunity to Mycobacterium tuberculosis in the mouse model. Subcutaneous administration of this vaccine provides equivalent protection to that of the live attenuated vaccine strain Bacille Calmette-Guérin (BCG). Protection is STING dependent but type I IFN independent and correlates with an increased frequency of a recently described subset of CXCR3-expressing T cells that localize to the lung parenchyma...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29699790/immunological-and-physical-evaluation-of-the-multistage-tuberculosis-subunit-vaccine-candidate-h56-caf01-formulated-as-a-spray-dried-powder
#7
Aneesh Thakur, Pall Thor Ingvarsson, Signe Tandrup Schmidt, Fabrice Rose, Peter Andersen, Dennis Christensen, Camilla Foged
Liquid vaccine dosage forms have limited stability and require refrigeration during their manufacture, distribution and storage. In contrast, solid vaccine dosage forms, produced by for example spray drying, offer improved storage stability and reduced dependence on cold-chain facilities. This is advantageous for mass immunization campaigns for global public health threats, e.g., tuberculosis (TB), and offers cheaper vaccine distribution. The multistage subunit vaccine antigen H56, which is a fusion protein of the Mycobacterium tuberculosis (Mtb) antigens Ag85B, ESAT-6, and Rv2660, has been shown to confer protective efficacy against active TB before and after Mtb exposure in preclinical models, and it is currently undergoing clinical phase 2a testing...
May 31, 2018: Vaccine
https://www.readbyqxmd.com/read/29687949/1-25-oh-2-d-3-inhibited-th17-cells-differentiation-via-regulating-the-nf-%C3%AE%C2%BAb-activity-and-expression-of-il-17
#8
Dong Sun, Fei Luo, Jun-Chao Xing, Fei Zhang, Jian-Zhong Xu, Ze-Hua Zhang
OBJECTIVES: The role of vitamin D (VD) in innate and adaptive immune responses to tuberculosis is still unclear. Our research was aimed to uncover the effect of VD on Th17 cells and elucidate potential molecular mechanism. MATERIALS AND METHODS: VDR-deficient and wild-type mice were used to obtain CD4 T cells. Th17 cells were induced and activated by Bacillus Calmette Guerin. Flow cytometry was used to analyse the apoptosis rate and degree of differentiation of Th17 cells in the treatment of 1,25(OH)2 D3 ...
April 24, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29684756/modulation-of-th1-tc1-and-th17-tc17-responses-in-pulmonary-tuberculosis-by-il-20-subfamily-of-cytokines
#9
Nathella Pavan Kumar, Kadar Moideen, Vaithilingam V Banurekha, Dina Nair, Subash Babu
Although IL-10 is known to be an important cytokine in the immune response to TB, very little is known about the role of IL-20 subfamily of cytokines in the host response to TB. To identify the role of CD4+ T and CD8+ T cells producing IL-20 subfamily of cytokines in human TB, we enumerated the frequencies of IL-10, IL-19 and IL-24 expressing CD4+ and CD8+ T cells following Mtb-specific antigen stimulation of cells from individuals with pulmonary TB (PTB) and latent TB (LTB). We first demonstrated that Mtb-specific antigen induce an expansion of CD4+ and CD8+ T cells expressing IL-10, IL-19 and IL-24 in PTB and LTB individuals, with frequencies being significantly higher in PTB...
August 2018: Cytokine
https://www.readbyqxmd.com/read/29681409/recombinant-bcg-rv2645-elicits-enhanced-protective-immunity-compared-to-bcg-in-vivo-with-induced-isgylation-related-genes-and-th1-and-th17-responses
#10
Wei Luo, Zilu Qu, Lingyun Zhang, Yan Xie, Fengling Luo, Yang Tan, Qin Pan, Xiao-Lian Zhang
There is a need to develop protective vaccines against tuberculosis (TB). Recently, we identified an immunodominant T-cell antigen, Rv2645, from the region of deletion 13 (RD13) of M. tuberculosis (M. tb) H37Rv, which is absent in Bacille Calmette-Guérin (BCG). Here, a recombinant BCG expressing Rv2645, namely, BCG::Rv2645, was constructed. Compared to BCG, we found that BCG::Rv2645 improved the antigen presentation capacity of dendritic cells (DCs) and elicited much stronger Th1 and Th17 responses, higher CD44high CD62low effector memory CD4+ T cells (TEM ), and fewer T regulated cells (Treg) and regulatory B10 in mice...
May 17, 2018: Vaccine
https://www.readbyqxmd.com/read/29618104/tissue-metabolic-changes-drive-cytokine-responses-to-mycobacterium-tuberculosis
#11
Ekta Lachmandas, Ana B Rios-Miguel, Valerie A C M Koeken, Eva van der Pasch, Vinod Kumar, Vasiliki Matzaraki, Yang Li, Marije Oosting, Leo A B Joosten, Richard A Notebaart, Mahdad Noursadeghi, Mihai G Netea, Reinout van Crevel, Gabriele Pollara
Cellular metabolism can influence host immune responses to Mycobacterium tuberculosis. Using a systems biology approach, differential expression of 292 metabolic genes involved in glycolysis, glutathione, pyrimidine, and inositol phosphate pathways was evident at the site of a human tuberculin skin test challenge in patients with active tuberculosis infection. For 28 metabolic genes, we identified single nucleotide polymorphisms that were trans-acting for in vitro cytokine responses to M. tuberculosis stimulation, including glutathione and pyrimidine metabolism genes that alter production of Th1 and Th17 cytokines...
June 5, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29593708/mucosal-delivery-of-fusion-proteins-with-bacillus-subtilis-spores-enhances-protection-against-tuberculosis-by-bacillus-calmette-gu%C3%A3-rin
#12
Alastair Copland, Gil R Diogo, Peter Hart, Shane Harris, Andy C Tran, Mathew J Paul, Mahavir Singh, Simon M Cutting, Rajko Reljic
Tuberculosis (TB) is the most deadly infectious disease in existence, and the only available vaccine, Bacillus Calmette-Guérin (BCG), is almost a century old and poorly protective. The immunological complexity of TB, coupled with rising resistance to antimicrobial therapies, necessitates a pipeline of diverse novel vaccines. Here, we show that Bacillus subtilis spores can be coated with a fusion protein 1 ("FP1") consisting of Mycobacterium tuberculosis (Mtb) antigens Ag85B, ACR, and HBHA. The resultant vaccine, Spore-FP1, was tested in a murine low-dose Mtb aerosol challenge model...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29554572/cytokine-and-soluble-adhesion-molecule-profiles-and-biomarkers-for-treatment-monitoring-in-re-treated-smear-positive-patients-with-pulmonary-tuberculosis
#13
Xue-Juan Bai, Hong-Min Li, You-Rong Yang, Jun-Xian Zhang, Yan Liang, Xue-Qiong Wu
Relapse of pulmonary tuberculosis (PTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis. Severe immunodeficiency or immune disorders may be the main reason for TB recurrence. This study aimed to quantify serum inflammatory cytokine and soluble adhesion molecule levels in Re-treated smear-positive PTB patients before and after re-anti-TB drug therapy. Serum samples were collected from 30 healthy controls and 215 Treated active PTB patients at baseline and 2, 4, and 6 months post-re-treatment...
August 2018: Cytokine
https://www.readbyqxmd.com/read/29554138/plga-particulate-subunit-tuberculosis-vaccines-promote-humoral-and-th17-responses-but-do-not-enhance-control-of-mycobacterium-tuberculosis-infection
#14
Anneliese S Ashhurst, Thaigarajan Parumasivam, John Gar Yan Chan, Leon C W Lin, Manuela Flórido, Nicholas P West, Hak-Kim Chan, Warwick J Britton
Tuberculosis places a staggering burden on human health globally. The new World Health Organisation End-TB Strategy has highlighted the urgent need for more effective TB vaccines to improve control of the disease. Protein-based subunit vaccines offer potential as safe and effective generators of protective immunity, and the use of particulate vaccine formulation and delivery by the pulmonary route may enhance local immunogenicity. In this study, novel particulate subunit vaccines were developed utilising biodegradable poly(lactic-co-glycolic acid) (PLGA) slow-release particles as carriers for the Mycobacterium tuberculosis lipoprotein MPT83, together with the adjuvants trehalose-dibehenate (TDB) or Monophosphoryl lipid A (MPL)...
2018: PloS One
https://www.readbyqxmd.com/read/29546381/human-immunodeficiency-virus-infection-impairs-th1-and-th17-mycobacterium-tuberculosis-specific-t-cell-responses
#15
Lyle W Murray, Iman Satti, Jodi Meyerowitz, Matthew Jones, Christian B Willberg, James E Ussher, Dominique Goedhals, Jacob Hurst, Rodney E Phillips, Helen McShane, Cloete van Vuuren, John Frater
Background: Human immunodeficiency virus (HIV)-infected individuals have a higher risk of developing active tuberculosis (TB) than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (Mtb)-specific CD4+ and CD8+ T-cell responses contributed to this increased risk. Methods: Mtb-specific T-cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa, were evaluated...
May 5, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29543912/tnf-%C3%AE-blockade-impairs-in-vitro-tuberculous-granuloma-formation-and-down-modulate-th1-th17-and-treg-cytokines
#16
Djalma A Alves da Silva, Marcos V da Silva, Cleyson C Oliveira Barros, Patrícia B Dias Alexandre, Rodolfo P Timóteo, Jonatas S Catarino, Helioswilton Sales-Campos, Juliana R Machado, Denise B R Rodrigues, Carlo J Oliveira, Virmondes Rodrigues
Tuberculosis (TB) is a granulomatous disease that has affected humanity for thousands of years. The production of cytokines, such as IFN-γ and TNF-α, is fundamental in the formation and maintenance of granulomas and in the control of the disease. Recently, the introduction of TNF-α-blocking monoclonal antibodies, such as Infliximab, has brought improvements in the treatment of patients with chronic inflammatory diseases, but this treatment also increases the risk of reactivation of latent tuberculosis. Our objective was to analyze, in an in vitro model, the influence of Infliximab on the granulomatous reactions and on the production of antigen-specific cytokines (TNF-α, IFN-γ, IL-12p40, IL-10 and IL-17) from beads sensitized with soluble Bacillus Calmette-Guérin (BCG) antigens cultured in the presence of peripheral blood mononuclear cells (PBMC) from TB patients...
2018: PloS One
https://www.readbyqxmd.com/read/29472922/efficacy-of-t-regulatory-cells-th17-cells-and-the-associated-markers-in-monitoring-tuberculosis-treatment-response
#17
Sonali Agrawal, Om Parkash, Alangudi Natarajan Palaniappan, Ashok Kumar Bhatia, Santosh Kumar, Devendra Singh Chauhan, M Madhan Kumar
Treatment monitoring is an essential aspect for tuberculosis (TB) disease management. Sputum smear microscopy is the only available tool for monitoring, but it suffers from demerits. Therefore, we sought to evaluate markers and cellular subsets of T regulatory (Treg) cells and T helper (Th) 17 cells in pulmonary TB patients (PTB) for TB treatment monitoring. Peripheral blood mononuclear cells (PBMCs) were stimulated in vitro (with purified protein derivative (PPD)) overnight which was followed by a polychromatic flow cytometry approach to study Treg and Th17 markers and cellular subsets in PTB ( n  = 12) undergoing antituberculous treatment (ATT)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29460733/influenza-vaccination-and-incident-tuberculosis-among-elderly-persons-taiwan-1
#18
Yung-Feng Yen, Sheng-Wei Pan, Vincent Yi-Fong Su, Pei-Hung Chuang, Jia-Yih Feng, Wei-Juin Su
Experimental studies have demonstrated that influenza vaccination may protect against tuberculosis (TB) through a Th17 response. This nationwide cohort study aimed to evaluate the association of influenza vaccination with incident TB among elderly persons in Taiwan. This 2005-2012 study included 99,982 elderly persons (64,290 vaccinated and 35,692 unvaccinated) from the Taiwan National Health Insurance Research Database. During the 738,367 person-years of follow-up, 1,141 (1.14%) persons had incident TB. The cumulative incidences of TB were 145...
March 2018: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29456692/effects-of-th17-treg-cell-imbalance-on-hiv-replication-in-patients-with-aids-complicated-with-tuberculosis
#19
Yanshuang Li, Weijia Sun
The purpose of this study was to determine the effect of Th17/Treg cell imbalance on HIV replication in patients with AIDS complicated with tuberculosis (TB). We selected 32 patients with AIDS combined with TB infection in our hospital and 30 healthy individual as controls. The Th17/Treg ratio in peripheral blood lymphocytes was detected by flow cytometry. Compared with healthy subjects, Th17 cells first declined in HIV patients with TB, but gradually increased over the course of the disease. Treg showed an increasing trend in HIV patients with TB...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29385117/t-cell-profile-was-altered-in-pulmonary-tuberculosis-patients-with-type-2-diabetes
#20
Xianhua Wang, Aiguo Ma, Xiuxia Han, Lei Chan, Hui Liang, Aishan Litifu, Feng Xue
BACKGROUND Studies have suggested that type 2 diabetes (T2D) increases the risk of active pulmonary tuberculosis (TB) infection. T2D might exacerbate TB severity and adversely impact the treatment of TB patients by suppressing the immune response of TB. However, how the immune cell profiles are changed in Chinese TB patients with coincident of T2D compared with TB patients without T2D is still unclear. MATERIAL AND METHODS To explore the immune cell profile alteration in TB patients with T2D, we collected blood samples from 46 TB patients with or without T2D and measured the profiles of T cell subsets...
January 31, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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