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Th17 tuberculosis

Joshua S Woodworth, Dennis Christensen, Joseph P Cassidy, Else Marie Agger, Rasmus Mortensen, Peter Andersen
T cell-mediated protection against Mycobacterium tuberculosis (Mtb) is dependent upon the ability to localize within the site of pulmonary infection and directly interact with infected cells. In turn, vaccine strategies to improve rapid T cell targeting of Mtb-infected cells after pulmonary exposure are being actively pursued. Given parenterally, the subunit vaccine H56:CAF01 elicits polyfunctional CD4 T cells that localize to the lung parenchyma and confer durable protection. Here, we find that airway mucosal boosting of parenteral H56:CAF01 immunization greatly enhances the population of long-lived lung-resident T cells (Trm) and increases early vaccine T cell responses to pulmonary Mtb challenge in multiple mouse models...
February 13, 2019: Mucosal Immunology
Aneesh Thakur, Cristina Rodríguez-Rodríguez, Katayoun Saatchi, Fabrice Rose, Tullio Esposito, Zeynab Nosrati, Peter Andersen, Dennis Christensen, Urs O Häfeli, Camilla Foged
Pulmonary tuberculosis (TB), which is caused by Mycobacterium tuberculosis ( Mtb) , remains a global pandemic, despite the widespread use of the parenteral live attenuated Bacillus Calmette-Guérin (BCG) vaccine during the past decades. Mucosal administration of next generation TB vaccines has great potential, but developing a safe and efficacious mucosal vaccine is challenging. Hence, understanding the in vivo biodistribution and pharmacokinetics of mucosal vaccines is essential for shaping the desired immune response and for optimal spatiotemporal targeting of the appropriate effector cells in the lungs...
2018: Frontiers in Immunology
Enzhuo Yang, Rui Yang, Ming Guo, Dan Huang, Wandang Wang, Zhuoran Zhang, Crystal Chen, Feifei Wang, Wenzhe Ho, Ling Shen, Heping Xiao, Zheng W Chen, Hongbo Shen
Tuberculosis (TB) has become the most deadly infectious diseases due to epidemics of HIV/AIDS and multidrug-resistant/extensively drug-resistant TB (MDR-/XDR-TB). Although person-to-person transmission contributes to MDR-TB, it remains unknown whether infection with MDR strains resembles infection with drug-sensitive (DS) TB strains, manipulating limited or broad immune responses. To address these questions, macaques were infected with MDR strain V791 and a drug-sensitive Erdman strain of TB. MDR bacilli burdens in the airway were significantly higher than those of the Erdman control after pulmonary exposure...
December 12, 2018: Emerging Microbes & Infections
Yanhua Liu, Ruo Wang, Jing Jiang, Zhihong Cao, Fei Zhai, Weiguo Sun, Xiaoxing Cheng
The role of primary subsets of DCs in Mycobacterium tuberculosis infection in humans is incompletely understood. In this study, we identified a CD1c DC subset with phenotype of CD1c+ CD11c+ CD19- CD11b+ that was significantly increased in tuberculous pleural effusions and in peripheral blood from patients with TB compared with that from healthy controls (p < 0.0001). Sputum smear/culture-positive patients with tuberculosis had significantly higher frequency of CD1c+ CD11b+ DC subset than sputum smear/culture-negative patients (p < 0...
December 2018: Tuberculosis
M P Cavalcanti-Neto, R Q Prado, A R Piñeros, C A Sérgio, T B Bertolini, A F Gembre, S G Ramos, V L Bonato
Given the impossibility to study the lung immune response during Mycobacterium tuberculosis-latent infection, and consequently, the mechanisms that control the bacterial load, it is reasonable to determine the activation of local immunity in the early phase of the infection. The phosphatidylinositol-3-kinase gamma enzyme (PI3Kγ) is involved in the leukocyte recruitment, phagocytosis and cellular differentiation, and therefore, it is considered a promising target for the development of immunotherapies for chronic inflammatory diseases...
December 2018: Tuberculosis
Alexiane Decout, Sandro Silva-Gomes, Daniel Drocourt, Emilyne Blattes, Michel Rivière, Jacques Prandi, Gérald Larrouy-Maumus, Anne-Marie Caminade, Beston Hamasur, Gunilla Källenius, Devinder Kaur, Karen M Dobos, Megan Lucas, Iain C Sutcliffe, Gurdyal S Besra, Ben J Appelmelk, Martine Gilleron, Mary Jackson, Alain Vercellone, Gérard Tiraby, Jérôme Nigou
Dectin-2 is a C-type lectin involved in the recognition of several pathogens such as Aspergillus fumigatus, Candida albicans, Schistosoma mansonii, and Mycobacterium tuberculosis that triggers Th17 immune responses. Identifying pathogen ligands and understanding the molecular basis of their recognition is one of the current challenges. Purified M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) was shown to induce signaling via Dectin-2, an activity that requires the (α1 → 2)-linked mannosides forming the caps...
November 15, 2018: Scientific Reports
Farzad Khademi, Mohammad Derakhshan, Arshid Yousefi-Avarvand, Adel Najafi, Mohsen Tafaghodi
BACKGROUND: Due to initiation of Mycobacterium tuberculosis infection via the mucosal tissue of the respiratory tract, intranasal administration of new tuberculosis vaccines is highly regarded to enhance mucosal immunity. Our outline was evaluation of mucosal and systemic immune responses in BALB/c mice after nasal delivery of HspX/EsxS fused antigen of Mycobacterium tuberculosis along with MPLA adjuvant entrapped in PLGA:DDA hybrid nanoparticles. METHODS: In this study, the double emulsion solvent evaporation method (w/o/w) was used to prepare different nanoparticle formulations containing HspX/EsxS protein and MPLA...
October 21, 2018: Microbial Pathogenesis
Laura Antonio-Herrera, Oscar Badillo-Godinez, Oscar Medina-Contreras, Araceli Tepale-Segura, Alberto García-Lozano, Lourdes Gutierrez-Xicotencatl, Gloria Soldevila, Fernando R Esquivel-Guadarrama, Juliana Idoyaga, Laura C Bonifaz
CD4+ T cells are major players in the immune response against several diseases; including AIDS, leishmaniasis, tuberculosis, influenza and cancer. Their activation has been successfully achieved by administering antigen coupled with antibodies, against DC-specific receptors in combination with adjuvants. Unfortunately, most of the adjuvants used so far in experimental models are unsuitable for human use. Therefore, human DC-targeted vaccination awaits the description of potent, yet nontoxic adjuvants. The nontoxic cholera B subunit (CTB) can be safely used in humans and it has the potential to activate CD4+ T cell responses...
2018: Frontiers in Immunology
Katharina Ronacher, Roma Sinha, Michelle Cestari
Approximately 10% of individuals latently infected with Mycobacterium tuberculosis (Mtb) develop active tuberculosis (TB) during their lifetime. Although it is well recognized that T-helper 1 immune responses are crucial for containing latent TB infection, the full array of host factors conferring protective immunity from TB progression are not completely understood. IL-22 is produced by cells of the innate and adaptive immune system including innate lymphoid cells, and natural killer cells as well as T lymphocytes (Th1, Th17, and Th22) and binds to its cognate receptor, the IL-22R1, which is expressed on non-hematopoietic cells such as lung epithelial cells...
2018: Frontiers in Immunology
Chaman Saini, Praveen Kumar, Mohd Tarique, Alpana Sharma, Venkatesh Ramesh
Background: The clinical forms of cutaneous tuberculosis (CTB) consist of a spectrum that reflects the host's immune response to Mycobacterium tuberculosis ; it provides an ideal model to study the immunological dysregulation in humans. IL-17 plays an important role in initial immune response and is involved in both immune-mediated protection and pathology during M. tuberculosis infection. TGF-β producing regulatory T-cells (Tregs) are high in leprosy patients and responsible for immune suppression...
2018: Journal of Inflammation Research
Asma Ahmed, Vasista Adiga, Soumya Nayak, J Anto Jesuraj Uday Kumar, Chirag Dhar, Pravat Nalini Sahoo, Bharath K Sundararaj, George D Souza, Annapurna Vyakarnam
Chronic T cell activation is a hallmark of pulmonary tuberculosis (PTB). The mechanisms underpinning this important phenomenon are however, poorly elucidated, though known to rely on control of T effector cells (Teff) by regulatory T cells (Treg). Our studies show that circulating natural Treg cells in adults with PTB preserve their suppressive potential but Teff cells from such subjects are resistant to Treg-mediated suppression. We found this to be due to expansion of an activated Teff subset identified by Human Leukocyte Antigen (HLA)-DR expression...
September 2018: PLoS Pathogens
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 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 the pathogenic mycobacterial cell wall. Immune parameters indicated that the adjuvant potency of PLG was statistically comparable to that of CFA and better than that of alum in the context of H1 antigen (Ag85B and ESAT-6 fusion)...
October 2018: Infection and Immunity
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
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
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
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
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
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
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 ...
October 2018: Cell Proliferation
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
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