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Tuberculosis immunity

Kerri M Malone, Kévin Rue-Albrecht, David A Magee, Kevin Conlon, Olga T Schubert, Nicolas C Nalpas, John A Browne, Alicia Smyth, Eamonn Gormley, Ruedi Aebersold, David E MacHugh, Stephen V Gordon
Members of the Mycobacterium tuberculosis complex (MTBC) are the causative agents of tuberculosis in a range of mammals, including humans. A key feature of MTBC pathogens is their high degree of genetic identity yet distinct host tropism. Notably, while Mycobacterium bovis is highly virulent and pathogenic for cattle, the human pathogen M. tuberculosis is attenuated in cattle. Previous research also suggests that host preference amongst MTBC members has a basis in host innate immune responses. To explore MTBC host tropism, we present in-depth profiling of the MTBC reference strains M...
March 20, 2018: Microbial Genomics
Rajeshwar Dayal, Dipti Agarwal, Rakesh Bhatia, C Bipin, Neeraj Kumar Yadav, Santosh Kumar, Shamrendra Narayan, Ankur Goyal
OBJECTIVES: To find out the prevalence of latent tuberculosis (TB) infection and TB disease among pediatric household contacts of adult drug resistant (MDR) and drug susceptible (DS) TB patients and to identify the risk factors for occurrence of TB infection in the contacts. METHODS: Pediatric household contacts (less than 15 y age) of adult TB patients (both MDR and DS) were included in the study. They were categorized as latent TB infection (LTBI), TB disease and TB exposed based on the results of tuberculin skin testing (TST), clinical examination and chest X-ray...
March 20, 2018: Indian Journal of Pediatrics
Feng Su, Xin Chen, Xin Liu, Guanghui Liu, Yong Zhang
Bovine tuberculosis is a disease caused by Mycobacterium bovis (M. bovis) that leads to great economic losses in cattle production. The discovery of a reasonable bioagent to reduce M. bovis infection risk and environment contamination becomes significant and urgent. Previous study reported that human β-defensin-3 (HBD3) participated in Mycobacterial immunity and was recognized as a suitable candidate reagent. However, its minimal inhibitory concentration to M. bovis is not yet reported. In this study, we first purified HBD3 protein by recombinant-DNA technology and prokaryotic expression system...
March 20, 2018: AMB Express
Tian Shen, Xingjian Cao, Junwei Shi, Yu Yu, Yihua Zhu, Delin Gu
BACKGROUND: Monocytes play a crucial role in immune response against Mycobacterium tuberculosis infection. The purpose of this current study was to investigate the morphology present on monocytes in peripheral blood from patients with active pulmonary tuberculosis (APTB) and the laboratory performance of the changes for discriminating cases from normal healthy subjects (NHS). METHOD: A total of 71 peripheral blood samples from patients with APTB, and 65 samples from NHS were analyzed...
March 16, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
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...
March 16, 2018: Cytokine
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
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
André Campaniço, Rui Moreira, Francisca Lopes
Tuberculosis (TB) remains a major health problem worldwide. The infectious agent, Mycobacterium tuberculosis, has a unique ability to survive within the host, alternating between active and latent disease states, and escaping the immune system defences. The extended duration of anti-TB regimens and the increasing prevalence of multidrug- (MDR) and extensively drug-resistant (XDR) M. tuberculosis strains have created an urgent need for new antibiotics active against drug-resistant organisms and that can shorten standard therapy...
March 9, 2018: European Journal of Medicinal Chemistry
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
Stefanie Kroeze, Pascale Ondoa, Cissy M Kityo, Margaret Siwale, Sulaimon Akanmu, Maureen Wellington, Marleen de Jager, Prudence Ive, Kishor Mandaliya, Wendy Stevens, T Sonia Boender, Marieke E de Pundert, Kim C E Sigaloff, Peter Reiss, Ferdinand W Wit, Tobias F Rinke de Wit, Raph L Hamers
OBJECTIVE: To assess incidence, determinants and clinical consequences of suboptimal immune recovery in HIV-1 infected adults in sub-Saharan Africa with sustained viral suppression on antiretroviral therapy (ART). DESIGN: Multi-country prospective cohort. METHODS: Suboptimal immune recovery was defined as proportions of participants who failed to attain clinically relevant CD4 cell count thresholds (>200, >350 and >500 cells/μL) despite sustained viral suppression on continuous first-line ART...
March 15, 2018: AIDS
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
Alain Bruno Tagne Nouemssi
Tuberculosis (TB) continues to represent an important public health challenge in the world and the USA, especially given its association with HIV infection and population migration. Cervical tuberculous lymphadenitis represents the most common extrapulmonary presentation of TB in the USA. Considerations for other causes of neck mass often contribute to delay in diagnosis. In this report, we describe the case of a 41-year-old man who presented with painful swelling of the neck and was diagnosed with tuberculous lymphadenitis, complicated by HIV therapy-associated immune reconstitution syndrome...
March 15, 2018: BMJ Case Reports
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
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