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M.tuberculosis immune

Bennett H Penn, Zoe Netter, Jeffrey R Johnson, John Von Dollen, Gwendolyn M Jang, Tasha Johnson, Yamini M Ohol, Cyrus Maher, Samantha L Bell, Kristina Geiger, Guillaume Golovkine, Xiaotang Du, Alex Choi, Trevor Parry, Bhopal C Mohapatra, Matthew D Storck, Hamid Band, Chen Chen, Stefanie Jäger, Michael Shales, Dan A Portnoy, Ryan Hernandez, Laurent Coscoy, Jeffery S Cox, Nevan J Krogan
Although macrophages are armed with potent antibacterial functions, Mycobacterium tuberculosis (Mtb) replicates inside these innate immune cells. Determinants of macrophage intrinsic bacterial control, and the Mtb strategies to overcome them, are poorly understood. To further study these processes, we used an affinity tag purification mass spectrometry (AP-MS) approach to identify 187 Mtb-human protein-protein interactions (PPIs) involving 34 secreted Mtb proteins. This interaction map revealed two factors involved in Mtb pathogenesis-the secreted Mtb protein, LpqN, and its binding partner, the human ubiquitin ligase CBL...
August 16, 2018: Molecular Cell
Manuela Flórido, Heni Muflihah, Leon C W Lin, Yingju Xia, Frederic Sierro, Mainthan Palendira, Carl G Feng, Patrick Bertolino, John Stambas, James A Triccas, Warwick J Britton
The lung is the primary site of infection with the major human pathogen, Mycobacterium tuberculosis. Effective vaccines against M. tuberculosis must stimulate memory T cells to provide early protection in the lung. Recently, tissue-resident memory T cells (TRM ) were found to be phenotypically and transcriptional distinct from circulating memory T cells. Here, we identified M. tuberculosis-specific CD4+ T cells induced by recombinant influenza A viruses (rIAV) vaccines expressing M. tuberculosis peptides that persisted in the lung parenchyma with the phenotypic and transcriptional characteristics of TRMs ...
August 16, 2018: Mucosal Immunology
Vanja P Ničković, Zorica N Vujnović-Živković, Rada Trajković, Dane Krtinić, Lidija Ristić, Milan Radović, Zorica Ćirić, Dušan Sokolović, Aleksandar M Veselinović
Tuberculosis is an ancient infectious disease, which re-emerged with the appearance of multidrug-resistant strains and Acquired Immune Deficiency Syndrome. Enoyl-acyl-carrier protein reductase (InhA) has emerged as a promising target for the development of antituberculosis therapeutics. The present study aims to develop quantitative structure-activity relationship (QSAR) models for a series of arylcarboxamides as InhA inhibitors. The QSAR models were calculated on the basis of optimal molecular descriptors based on the simplified molecular-input line-entry system (SMILES) notation with the Monte Carlo method as a model developer...
August 13, 2018: Journal of Biomolecular Structure & Dynamics
Naomi C Bull, Daryan A Kaveh, M C Garcia-Pelayo, Elena Stylianou, Helen McShane, Philip J Hogarth
Tuberculosis (TB) is the biggest cause of human mortality from an infectious disease. The only vaccine currently available, bacille Calmette-Guérin (BCG), demonstrates some protection against disseminated disease in childhood but very variable efficacy against pulmonary disease in adults. A greater understanding of protective host immune responses is required in order to aid the development of improved vaccines. Tissue-resident memory T cells (TRM ) are a recently-identified subset of T cells which may represent an important component of protective immunity to TB...
August 7, 2018: Vaccine
Odin Goovaerts, Pauline N M Mwinzi, Erick M O Muok, Ann Ceulemans, Robert Colebunders, Luc Kestens
BACKGROUND: Among the different faces of immune reconstitution inflammatory syndrome (IRIS) developing in HIV-patients, no clinical definition has been reported for Schistosomiasis-IRIS (Schisto-IRIS). Although Schisto-IRIS remains largely uninvestigated, matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have previously been associated with S. mansoni infection and tuberculosis-IRIS. Here, we aimed to investigate the relevance of these markers in Schisto-IRIS...
August 8, 2018: PLoS Neglected Tropical Diseases
Juliane Radloff, Jan Heyckendorf, Lize van der Merwe, Patricia Sanchez Carballo, Norbert Reiling, Elvira Richter, Christoph Lange, Barbara Kalsdorf
Background: In order to eliminate tuberculosis (TB), an effective vaccine is urgently needed to prevent infection with Mycobacterium tuberculosis . A key obstacle for the development of novel TB vaccines is the lack of surrogate markers for immune protection against M. tuberculosis . Methods: We investigated growth rates of M. tuberculosis in the mycobacterial growth inhibition assay (MGIA) as a marker for mycobacterial growth control of human bronchoalveolar lavage (BALC) and peripheral blood mononuclear cells (PBMC) before and after vaccination with Mycobacterium bovis Bacille Calmette-Guérin (BCG) of healthy adult volunteers...
2018: Frontiers in Immunology
Xiaolei Wang, Xiaowei Tang, Zheng Zhou, Qing Huang
Interleukin (IL)-10 plays a key role in immune response following mycobacterial infection, which can be inhibited by histone deacetylase (HDAC) 6. In this study, we explored whether Tubastatin A, a HDAC6 inhibitor, could enhance immune response and restrain mycobacterial growth. We established a mouse model using attenuated Mycobacterium tuberculosis (M.tbH37Ra) infection. The growth of mycobacteria was evaluated using colony form unit assays. Immune response statues were investigated using flow cytometry. Chromatin immunoprecipitation was used to study the influence of HDAC6 on IL10 transcription...
July 31, 2018: Pathogens and Disease
M Martini, F Paluan
Between nineteenth and twentieth centuries, medicine knew the beginning of an incessant development: the birth of new medical specialties (radiology, for instance), the introduction of new devices in medical and surgical wards, and the discovery of bacteria represented important milestones in that first historical period. The Medical School of the University of Genoa, head by Edoardo Maragliano, full professor of internal medicine, took on a relevant role in the battle against tuberculosis, through the experimental demonstration of the existence of an immune response against M...
June 2018: Journal of Preventive Medicine and Hygiene
Harsha Anuruddhika Dissanayake, Praveen Nilendra Weeratunga, Panduka Karunanayake, Rushika D Lanerolle, M V Chandu de Silva, Saroj Jayasinghe
BACKGROUND: Aspergillosis is a serious infection particularly affecting the immunodeficient host. Its co-infection with tuberculosis and cytomegalovirus has not been reported before. Embolic events are well recognized with aspergillous endocarditis and aortitis. Splenic abscess is a rare serious complication of disseminated aspergillosis and is difficult to treat. We report the first case of multiple embolic events and splenic abscess in a patient with pulmonary aspergillosis and cytomegaloviral and tuberculous co-infection, without endocarditis or aortitis...
August 6, 2018: BMC Infectious Diseases
M D Johansen, K de Silva, K M Plain, D J Begg, R J Whittington, A C Purdie
Pathogenic mycobacteria such as Mycobacterium tuberculosis are capable of utilising cholesterol as a primary carbon-based energy source in vitro but there has been little research examining the significance of cholesterol in vivo. Johne's disease is a chronic enteric disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). This study sought to evaluate the levels of total serum cholesterol in the host following exposure to MAP. Blood samples were collected from both sheep and cattle prior to experimental challenge with MAP and at monthly intervals post-challenge...
August 2018: Veterinary Immunology and Immunopathology
Andrew J Olive, Clare M Smith, Michael C Kiritsy, Christopher M Sassetti
Protection from infectious disease relies on two distinct strategies: antimicrobial resistance directly inhibits pathogen growth, whereas infection tolerance protects from the negative impact of infection on host health. A single immune mediator can differentially contribute to these strategies in distinct contexts, confounding our understanding of protection to different pathogens. For example, the NADPH-dependent phagocyte oxidase (Phox) complex produces antimicrobial superoxide and protects from tuberculosis (TB) in humans...
July 30, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Hsin-Chih Lai, Chih-Jung Chang, Chuan-Sheng Lin, Tsung-Ru Wu, Ya-Jing Hsu, Ting-Shu Wu, Jang-Jih Lu, Jan Martel, David M Ojcius, Cheng-Lung Ku, John D Young, Chia-Chen Lu
In developed countries, pulmonary nontuberculous mycobacteria (NTM) infections are more prevalent than Mycobacterium tuberculosis infections. Given the differences in the pathogenesis of NTM and M. tuberculosis infections, separate studies are needed to investigate the pathological effects of NTM pathogens. Our previous study showed that anti-IFN-γ autoantibodies are detected in NTM-infected patients. However, the role of NK cells and especially NK cell-derived IFN-γ in this context has not been studied in detail...
July 30, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
M Mohammadi Tashakkori, M Tabatabaei, M Tebianian, N Mosavari
Tuberculosis (TB) is a zoonotic infectious disease common to humans and animals which has been caused by a rod shaped, acid fast bacterium, called Mycobacterium bovis . The rapid and sensitive detection is a great challenge for TB diagnosis. The virulent strains of Mycobacterium tuberculosis complex (MTBC) have 16 different regions of difference (RD) in their genome which encode some important antigens. The major protein of M. bovis 64 (MPT-64) is one of the main immune-stimulating antigens which are encode by RD-2 region...
2018: Iranian Journal of Veterinary Research
Mariana Salgado-Bustamante, Ana K Rocha-Viggiano, César Rivas-Santiago, Martín Magaña-Aquino, Jesús A López, Yamilé López-Hernández
Tuberculosis (TB) and diabetes mellitus Type 2 (DM2) are two diseases as ancient as they are harmful to human health. The outcome for both diseases in part depends on immune and metabolic individual responses. DM2 is increasing yearly, mainly due to environmental, genetic and lifestyle habits. There are multiple evidence that DM2 is one of the most important risk factor of becoming infected with TB or reactivating latent TB. Mass spectrometry-based metabolomics is an important tool for elucidating the metabolites and metabolic pathways that influence the immune responses to M...
July 25, 2018: Biomarkers in Medicine
Supriya Shukla, Edward T Richardson, Michael G Drage, W Henry Boom, Clifford V Harding
Mycobacterium tuberculosis (Mtb) causes persistent infection due to its ability to evade host immune responses. Mtb induces Toll-like receptor 2 (TLR2) signaling, which influences immune responses to Mtb. TLR2 agonists expressed by Mtb include lipoproteins (e.g. LprG), the glycolipid phosphatidylinositol mannoside 6 (PIM6), and the lipoglycan lipomannan (LM). Another Mtb lipoglycan, mannose-capped lipoarabinomannan (ManLAM), lacks TLR2 agonist activity. In contrast, PILAM from M. smegmatis does have TLR2 agonist activity...
July 23, 2018: Infection and Immunity
K Afsal, P Selvaraj, M Harishankar
1,25-dihydroxyvitaminD3 [1,25(OH)2 D3 ] modulates both the innate and adaptive immunity in tuberculosis. We explored the effect of 1,25(OH)2 D3 on cytolytic molecules like perforin, granulysin, and granzyme-B in T-cells and natural killer cells during M. tuberculosis (Mtb) infection. Peripheral blood mononuclear cells (PBMCs) from 45 healthy controls (HCs) and 45 pulmonary tuberculosis (PTB) patients were cultured with Mtb in the absence or presence of 1,25(OH)2 D3 for 72 h. The percentage of perforin, granulysin, and granzyme-B positive cells were estimated by flow cytometry...
September 2018: International Immunopharmacology
Harish Shukla, Shaheb Raj Khan, Rohit Shukla, Manju Yasoda Krishnan, Md Sohail Akhtar, Timir Tripathi
Ascorbate has been demonstrated to interfere with the growth of Mycobacterium tuberculosis. It scavenges oxygen in the culture medium to induce dormancy of M. tuberculosis. It kills the mycobacteria by generating reactive oxygen intermediates via iron mediated Fenton reactions. In this study, we observed that ascorbate can inhibit M. tuberculosis isocitrate lyase (MtbICL) with an IC50 of 2.15 mΜ. MtbICL is an essential enzyme for the survival of M. tuberculosis under dormancy. We studied the effect of ascorbate on the growth of M...
July 2018: Tuberculosis
Landry Blanc, Jansy Passiflora Sarathy, Nadine Alvarez Cabrera, Paul O'Brien, Isabela Dias-Freedman, Marizel Mina, James Sacchettini, Radojka M Savic, Martin Gengenbacher, Brendan K Podell, Brendan Prideaux, Thomas Ioerger, Thomas Dick, Véronique Dartois
In the 1970s, inclusion of pyrazinamide (PZA) in the drug regimen of tuberculosis (TB) patients for the first 2 mo achieved a drastic reduction of therapy duration. Until now, however, the mechanisms underlying PZA's unique contribution to efficacy have remained controversial, and animal efficacy data vary across species. To understand how PZA kills bacterial populations present in critical lung lesion compartments, we first characterized a rabbit model of active TB, showing striking similarities in lesion types and fates to nonhuman primate models deemed the most appropriate surrogates of human TB...
August 6, 2018: Journal of Experimental Medicine
Miao-Hsi Hsieh, Chih-Ying Ou, Wen-Yu Hsieh, Hui-Fang Kao, Shih-Wei Lee, Jiu-Yao Wang, Lawrence S H Wu
Surfactant proteins (SPs)-A and -D are C-type lectins of the collectin family and function in the clearance of infectious particles in the lungs. Some polymorphisms of SPs that give rise to amino acid changes have been found to affect their function. Several SP-A gene polymorphisms have been reported to be associated with respiratory infection diseases, such as tuberculosis (TB). However, the relationship between surfactant proteins D (SP-D) polymorphisms and TB is still unclear. To study the associations between SP-D polymorphisms and TB, the correlations of SP-D polymorphisms with TB were examined in a case-control study, which included 364 patients with TB and 177 control subjects...
2018: Frontiers in Immunology
Louis S Ates, Anzaan Dippenaar, Fadel Sayes, Alexandre Pawlik, Christiane Bouchier, Laurence Ma, Robin M Warren, Wladimir Sougakoff, Laleh Majlessi, Jeroen W J van Heijst, Florence Brossier, Roland Brosch
Mycobacterium africanum consists of Lineages L5 and L6 of the Mycobacterium tuberculosis complex (MTBC) and causes human tuberculosis in specific regions of Western Africa, but is generally not transmitted in other parts of the world. Since M. africanum is evolutionarily closely placed between the globally dispersed Mycobacterium tuberculosis and animal-adapted MTBC-members, these lineages provide valuable insight into M. tuberculosis evolution. Here, we have collected 15 M. africanum L5 strains isolated in France over 4 decades...
August 1, 2018: Genome Biology and Evolution
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