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M.tuberculosis immune

Nida Mubin, Mohd Saad Umar, Swaleha Zubair, Mohammad Owais
In the present study, we investigated potential of chitosan-based nanoparticles (CNPs) to deliver loaded therapeutic molecules to pathogen harboring macrophages. We fabricated stable CNPs employing ionic cross-linking method and evaluated their potential to target RAW 264.7 cells. The physicochemical characterization of as-synthesized CNPs was determined using electron microscopy, infrared microscopy and zeta potential measurement. Next, cellular uptake and intracellular localization studies of CNPs were followed in living RAW264...
2018: Frontiers in Microbiology
Jiansong Tang, Yi Cai, Jianguo Liang, Zhiwu Tan, Xian Tang, Chi Zhang, Lin Cheng, Jingying Zhou, Haibo Wang, Wing-Cheong Yam, Xinchun Chen, Hui Wang, Zhiwei Chen
DNA vaccines have been extensively studied as preventative and therapeutic interventions for various infectious diseases such as tuberculosis, HIV/AIDS and influenza. Despite promising progresses made, improving the immunogenicity of DNA vaccine remains a technical challenge for clinical development. In this study, we investigated a tuberculosis DNA vaccine BERopt , which contained a codon-optimized fusion immunogen Ag85B-ESAT-6-Rv2660c for enhanced mammalian cell expression and immunogenicity. BERopt immunization through in vivo electroporation in BALB/c mice induced surprisingly high frequencies of Ag85B tetramer+ CD8+ T cells in peripheral blood and IFN-γ-secreting CD8+ T cells in splenocytes...
December 2018: Tuberculosis
César Pedroza-Roldán, Brenda Marquina-Castillo, Dulce Mata-Espinosa, Jorge Barrios-Payán, Michel de Jesús Aceves-Sánchez, Rogelio Hernández Pando, Mario Alberto Flores-Valdez
Mycobacterium tuberculosis remains as a threat to public health around the world with 1.7 million cases of TB-associated deaths during 2016. Despite the use of Bacillus Calmette-Guerin (BCG) vaccine, control of the infection has not been successful. Because of this, several efforts have been made in order to develop new vaccines capable of boosting previous immunization or attempted for replacing current BCG. We previously showed that over expression of the M. tuberculosis adenylyl cyclase encoding gene Rv2212 in BCG bacilli (BCG-Rv2212), induced an attenuated phenotype when administered in BALB/c mice...
December 2018: Tuberculosis
Tatiana K Kondratieva, Marina A Kapina, Elvira I Rubakova, Elena V Kondratieva, Boris V Nikonenko, Konstantin B Majorov, Alexander V Dyatlov, Irina A Linge, Alexander S Apt
TB infection in mice develops relatively rapidly which interferes with experimental dissection of immune responses and lung pathology features that differ between genetically susceptible and resistant hosts. Earlier we have shown that the M. tuberculosis strain lacking four of five Rpf genes (ΔACDE) is seriously attenuated for growth in vivo. Using this strain, we assessed key parameters of lung pathology, immune and inflammatory responses in chronic and reactivation TB infections in highly susceptible I/St and more resistant B6 mice...
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
Mark R Cronan, Molly A Matty, Allison F Rosenberg, Landry Blanc, Charlie J Pyle, Scott T Espenschied, John F Rawls, Véronique Dartois, David M Tobin
A central and critical structure in tuberculosis, the mycobacterial granuloma consists of highly organized immune cells, including macrophages that drive granuloma formation through a characteristic epithelioid transformation. Difficulties in imaging within intact animals and caveats associated with in vitro assembly models have severely limited the study and experimental manipulation of mature granulomas. Here we describe a new ex vivo culture technique, wherein mature, fully organized zebrafish granulomas are microdissected and maintained in three-dimensional (3D) culture...
December 2018: Nature Methods
Vladimir Lopez, Elisabeth van der Heijden, Margarita Villar, Anita Michel, Pilar Alberdi, Christian Gortázar, Victor Rutten, José de la Fuente
There is an imperative need for effective control of bovine tuberculosis (BTB) on a global scale and vaccination of cattle may prove to be pivotal in achieving this. The oral and parenteral use of a heat-inactivated Mycobacterium bovis (M. bovis) vaccine has previously been found to confer partial protection against BTB in several species. A role for complement factor C3 has been suggested in wild boar, but the exact mechanism by which this vaccine provides protection remains unclear. In the present study, a quantitative proteomics approach was used to analyze the white blood cell proteome of vaccinated cattle in comparison to unvaccinated controls, prior (T0) and in response to vaccination, skin test and challenge (T9 and T12)...
December 2018: Veterinary Immunology and Immunopathology
Sandrine Lesellier
Mycobacterium bovis is the main cause of bovine tuberculosis and its eradication is proving difficult in many countries because of wildlife reservoirs, including European badgers (Meles meles) in the UK Ireland. Following the development of badger specific immunological reagents, many studies have shown that some aspects of the cellular and serological immune responses of badgers to virulent M. bovis and the attenuated M. bovis BCG (Bacille of Calmette and Guérin) strain are similar to those seen in other animal hosts infected with M...
December 2018: Comparative Immunology, Microbiology and Infectious Diseases
Alexia Dumas, Dan Corral, André Colom, Florence Levillain, Antonio Peixoto, Denis Hudrisier, Yannick Poquet, Olivier Neyrolles
Tuberculosis (TB), caused by the airborne bacterial pathogen Mycobacterium tuberculosis , remains a major source of morbidity and mortality worldwide. So far, the study of host-pathogen interactions in TB has mostly focused on the physiology and virulence of the pathogen, as well as, on the various innate and adaptive immune compartments of the host. Microbial organisms endogenous to our body, the so-called microbiota, interact not only with invading pathogens, but also with our immune system. Yet, the impact of the microbiota on host defense against M...
2018: Frontiers in Immunology
Elouise E Kroon, Anna K Coussens, Craig Kinnear, Marianna Orlova, Marlo Möller, Allison Seeger, Robert J Wilkinson, Eileen G Hoal, Erwin Schurr
Certain individuals are able to resist Mycobacterium tuberculosis infection despite persistent and intense exposure. These persons do not exhibit adaptive immune priming as measured by tuberculin skin test (TST) and interferon-γ (IFN-γ) release assay (IGRA) responses, nor do they develop active tuberculosis (TB). Genetic investigation of individuals who are able to resist M. tuberculosis infection shows there are likely a combination of genetic variants that contribute to the phenotype. The contribution of the innate immune system and the exact cells involved in this phenotype remain incompletely elucidated...
2018: Frontiers in Immunology
Pierre Santucci, Vanessa Point, Isabelle Poncin, Alexandre Guy, Céline Crauste, Carole Serveau-Avesque, Jean Marie Galano, Christopher D Spilling, Jean François Cavalier, Stéphane Canaan
Tuberculosis caused by Mycobacterium tuberculosis is currently one of the leading causes of death from an infectious agent. The main difficulties encountered in eradicating this bacteria are mainly related to i) a very complex lipid composition of the bacillus cell wall, ii) its ability to hide from the immune system inside the granulomas, and iii) the increasing number of resistant strains. In this context, we were interested in the Rv0646c ( lipGMTB ) gene located upstream to the mmaA cluster which is described as being crucial for the production of cell-wall components and required for the bacilli adaptation and survival in mouse macrophages ...
November 28, 2018: Bioscience Reports
Isabel Sada-Ovalle, Leslie Chávez-Galán, Luis Vasquez, Stepahnie Aldriguetti, Irma Rosas-Perez, Alejandra Ramiréz-Venegas, Rogelio Perez-Padilla, Luis Torre-Bouscoulet
Use of solid fuels for cooking or home heating has been related to various diseases of the respiratory tract. Woodsmoke contains a mixture of carcinogenic polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds. Inhalation of these materials induces local and systemic changes in the immune system which may impair critical cell defense mechanisms; however, few studies have investigated the early effects that PAH exposures have on immune cells as macrophages. The aim of this study was to analyze if the pre-exposure to PAHs derived from woodsmoke deteriorates macrophage ability to control the intracellular growth of Mycobacterium tuberculosis ...
2018: Frontiers in Medicine
Noëmi R Meier, Marc Jacobsen, Tom H M Ottenhoff, Nicole Ritz
Background: Current immunodiagnostic tests for tuberculosis (TB) are based on the detection of an immune response toward mycobacterial antigens injected into the skin or following an in-vitro simulation in interferon gamma-release assays. Both tests have limited sensitivity and are unable to differentiate between tuberculosis infection (LTBI) and active tuberculosis disease (aTB). To overcome this, the use of novel Mycobacterium tuberculosis ( M. tuberculosis) stage-specific antigens for the diagnosis of LTBI and aTB has gained interest in recent years...
2018: Frontiers in Immunology
N N You, Q Liu, L M Zhu, W Lu
Tuberculosis (TB) is a serious infectious diseases threating human health, bacillus balmette-guerin vaccine (BCG) is the only available TB vaccine now, neonatal vaccination can significantly reduce the incidence and death of tuberculosis. However, due to its limited protection period, one dose vaccination after birth does not have a protective effect for adolescents and adults. Therefore, how to reduce the prevalence of TB in adolescents and adults effectively is essential for TB prevention and control. In this paper, we reviewed the literature from PubMed, CNKI, and Wanfang database to analyze and summarize the characteristics of BCG vaccine, immune effects and immunity endurance, the effects of BCG vaccination and repeated BCG vaccination in adolescents adults and discuse the change of attitude and trends of BCG use in the three documents issued by the World Health Organization on position of BCG...
November 10, 2018: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
Sarah R Elliott, Dylan W White, Anna D Tischler
The Mycobacterium tuberculosis Type VII secretion system ESX-5, which has been implicated in virulence, is activated at the transcriptional level by the phosphate starvation responsive Pst/SenX3-RegX3 signal transduction system. Deletion of pstA1 , which encodes a Pst phosphate transporter component, causes constitutive activation of the response regulator RegX3, hyper-secretion of ESX-5 substrates and attenuation in the mouse infection model. We hypothesized that constitutive activation of ESX-5 secretion causes attenuation of the Δ pstA1 mutant...
November 19, 2018: Infection and Immunity
Michele Tomasicchio, Malika Davids, Anil Pooran, Grant Theron, Liezel Smith, Lynn Semple, Richard Meldau, Janet Patricia Hapgood, Keertan Dheda
Background: The effects of the widely used progestin-only injectable contraceptives, medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A), on host susceptibility to Mycobacterium tuberculosis (M.tb) are unknown. Methods: We recruited HIV uninfected females, not taking any contraceptives, from Cape Town, South Africa, to evaluate the effect of MPA, NET-A, dexamethasone on M.tb containment in monocyte-derived macrophages (MDMs) co-incubated with purified protein derivative (PPD)-driven peripheral blood-derived effector cells...
November 19, 2018: Journal of Infectious Diseases
N C Bull, E Stylianou, D A Kaveh, N Pinpathomrat, J Pasricha, R Harrington-Kandt, M C Garcia-Pelayo, P J Hogarth, H McShane
BCG, the only vaccine licensed against tuberculosis, demonstrates variable efficacy in humans. Recent preclinical studies highlight the potential for mucosal BCG vaccination to improve protection. Lung tissue-resident memory T cells reside within the parenchyma, potentially playing an important role in protective immunity to tuberculosis. We hypothesised that mucosal BCG vaccination may enhance generation of lung tissue-resident T cells, affording improved protection against Mycobacterium tuberculosis. In a mouse model, mucosal intranasal (IN) BCG vaccination conferred superior protection in the lungs compared to the systemic intradermal (ID) route...
November 16, 2018: Mucosal Immunology
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
Carlos Franco-Paredes, Luis A Marcos, Andrés F Henao-Martínez, Alfonso J Rodríguez-Morales, Wilmer E Villamil-Gómez, Eduardo Gotuzzo, Alexandro Bonifaz
SUMMARYHumans encounter mycobacterial species due to their ubiquity in different environmental niches. In many individuals, pathogenic mycobacterial species may breach our first-line barrier defenses of the innate immune system and modulate the activation of phagocytes to cause disease of the respiratory tract or the skin and soft tissues, sometimes resulting in disseminated infection. Cutaneous mycobacterial infections may cause a wide range of clinical manifestations, which are divided into four main disease categories: (i) cutaneous manifestations of Mycobacterium tuberculosis infection, (ii) Buruli ulcer caused by Mycobacterium ulcerans and other related slowly growing mycobacteria, (iii) leprosy caused by Mycobacterium leprae and Mycobacterium lepromatosis , and (iv) cutaneous infections caused by rapidly growing mycobacteria...
January 2018: Clinical Microbiology Reviews
Landry Blanc, Isaac B Daudelin, Brendan K Podell, Pei-Yu Chen, Matthew Zimmerman, Amanda J Martinot, Rada M Savic, Brendan Prideaux, Véronique Dartois
Understanding the distribution patterns of antibiotics at the site of infection is paramount to selecting adequate drug regimens and developing new antibiotics. Tuberculosis (TB) lung lesions are made of various immune cell types, some of which harbor persistent forms of the pathogen, Mycobacterium tuberculosis . By combining high resolution MALDI MSI with histology staining and quantitative image analysis in rabbits with active TB, we have mapped the distribution of a fluoroquinolone at high resolution, and identified the immune-pathological factors driving its heterogeneous penetration within TB lesions, in relation to where bacteria reside...
November 14, 2018: ELife
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