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macrophages tuberculosis

Ludmylla Cunha, Ana M Rosa da Costa, João P Lourenço, Francesca Buttini, Ana Grenha
Pulmonary tuberculosis accounts for 80% of cases and the delivery of antitubercular drugs into the lungs allows targeting the infected organ and, possibly, reducing systemic drug toxicity. This work aimed at using fucoidan as matrix of inhalable microparticles that associate two first-line antitubercular drugs, for an application in pulmonary tuberculosis therapy. Fucoidan is composed of fucose and sulphated sugar residues, moieties described as being recognised by surface receptors of alveolar macrophages, which host mycobacteria...
August 16, 2018: Journal of Microencapsulation
Siti Kurniawati, Soedarsono Soedarsono, Aulanni'am Aulanni'am, Ni Made Mertaniasih
Background: Mycobacterium tuberculosis Complex (MTBC) is a group of Mycobacterium that causes tuberculosis (TB). TB is an infectious disease that remains a global health problem. Indonesia is one of the five countries in the world where TB is the most prevalent and became the country with tle second largest rate of TB in 2014 and 2015. MTBC has high pathogenicity that can cause infections in animals and humans. The most common route of transmission is via airborne droplet nuclei and contact with animals or humans infected with TB...
2018: African Journal of Infectious Diseases
Ram Prasad Bhusal, Krunal Patel, Brooke X C Kwai, Anne Swartjes, Ghader Bashiri, Jóhannes Reynisson, Jonathan Sperry, Ivanhoe K H Leung
The enzymes isocitrate lyase (ICL) isoforms 1 and 2 are essential for Mycobacterium tuberculosis survival within macrophages during latent tuberculosis (TB). As such, ICLs are attractive therapeutic targets for the treatment of tuberculosis. However, there are few biophysical assays that are available for accurate kinetic and inhibition studies of ICL in vitro . Herein we report the development of a combined NMR spectroscopy and thermal shift assay to study ICL inhibitors for both screening and inhibition constant (IC50 ) measurement...
November 1, 2017: MedChemComm
Benoit Allard, Alice Panariti, James G Martin
Pathogen persistence in the respiratory tract is an important preoccupation, and of particular relevance to infectious diseases such as tuberculosis. The equilibrium between elimination of pathogens and the magnitude of the host response is a sword of Damocles for susceptible patients. The alveolar macrophage is the first sentinel of the respiratory tree and constitutes the dominant immune cell in the steady state. This immune cell is a key player in the balance between defense against pathogens and tolerance toward innocuous stimuli...
2018: Frontiers in Immunology
Pavithra Sampath, Kadar Moideen, Uma Devi Ranganathan, Ramalingam Bethunaickan
Monocytes are critical defense components that play an important role in the primary innate immune response. The heterogeneous nature of monocytes and their ability to differentiate into either monocyte-derived macrophages or monocyte-derived dendritic cells allows them to serve as a bridge between the innate and adaptive immune responses. Current studies of monocytes based on immunofluorescence, single-cell RNA sequencing and whole mass spectrometry finger printing reveals different classification systems for monocyte subsets...
2018: Frontiers in Immunology
P C Gaspar, R C M Rudolf-Oliveira, L M Wildner, A C R de Moraes, M L Reis, R M da Silva, J Gonçalves, M L Bazzo, M C Santos-Silva
SETTING: Information about the sputum cells of pulmonary tuberculosis (PTB) patients is scarce. The analysis of sputum cells using optical microscopy (OM) is a well-established method, but it has some serious limitations. OBJECTIVE: To establish a new flow cytometry (FC) protocol for the leucocyte evaluation of sputum samples from PTB patients. DESIGN: A new FC protocol using 0.1% dithiothreitol and 0.5% paraformaldehyde was developed to fluidise sputum samples and kill Mycobacterium tuberculosis, respectively, to allow the analysis of sputum samples collected from TB patients...
September 1, 2018: International Journal of Tuberculosis and Lung Disease
Ashutosh Upadhyay, Santosh Kumar, Steven A Rooker, Jordan T Koehn, Debbie C Crans, Michael R McNeil, J Shaun Lott, Dean C Crick
MenJ, annotated as an oxidoreductase, was recently demonstrated to catalyze the reduction (saturation) of a single double bond in the isoprenyl side-chain of mycobacterial menaquinone. This modification was shown to be essential for bacterial survival in J774A.1 macrophage-like cells suggesting that MenJ may be a conditional drug target in Mycobacterium tuberculosis and other pathogenic mycobacteria. Recombinant protein was expressed in a heterologous host and the activity was characterized. Although highly regiospecific in vivo, the activity is not absolutely regiospecific in vitro; in addition, the enzyme is not specific for naphthoquinones vs benzoquinones...
August 9, 2018: ACS Chemical Biology
Prasenjit Das, Ritika Rampal, Sonakshi Udinia, Tarun Kumar, Sucharita Pilli, Nahid Wari, Imtiaz Khan Ahmed, Saurabh Kedia, Siddhartha Datta Gupta, Dhiraj Kumar, Vineet Ahuja
Background/Aims: Classical M1 macrophage activation exhibits an inflammatory phenotype while alternative M2 macrophage activation exhibits an anti-inflammatory phenotype. We aimed to determine whether there are discriminant patterns of macrophage polarization in Crohn's disease (CD) and intestinal tuberculosis (iTB). Methods: Colonic mucosal biopsies from 29 patients with iTB, 50 with CD, and 19 controls were examined. Dual colored immunohistochemistry was performed for iNOS/CD68 (an M1φ marker) and CD163/CD68 (an M2φ marker), and the ratio of M1φ to M2φ was assessed...
July 2018: Intestinal Research
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
Nathan D Hicks, Jian Yang, Xiaobing Zhang, Bing Zhao, Yonatan H Grad, Liguo Liu, Xichao Ou, Zhili Chang, Hui Xia, Yang Zhou, Shengfen Wang, Jie Dong, Lilian Sun, Yafang Zhu, Yanlin Zhao, Qi Jin, Sarah M Fortune
The global epidemic of drug-resistant tuberculosis is a catastrophic example of how antimicrobial resistance is undermining the public health gains made possible by combination drug therapy. Recent evidence points to unappreciated bacterial factors that accelerate the emergence of drug resistance. In a genome-wide association study of Mycobacterium tuberculosis isolates from China, we find mutations in the gene encoding the transcription factor prpR enriched in drug-resistant strains. prpR mutations confer conditional drug tolerance to three of the most effective classes of antibiotics by altering propionyl-CoA metabolism...
August 6, 2018: Nature Microbiology
Federico Fenaroli, Urska Repnik, Yitian Xu, Kerstin Johann, Simon Van Herck, Pradip Dey, Frode Miltzow Skjeldal, Dominik M Frei, Shahla Bagherifam, Agnese Kocere, Rainer Haag, Bruno G De Geest, Matthias Barz, David G Russell, Gareth Griffiths
The enhanced permeability and retention (EPR) effect is the only described mechanism enabling nanoparticles (NP) flowing in blood to reach tumours by a passive targeting mechanism. Here, using the transparent zebrafish model infected with Mycobacterium marinum we show that an EPR-like process also occurs allowing different types of NP to extravasate from the vasculature to reach granulomas that assemble during tuberculosis (TB) infection. PEGylated liposomes and other NP types cross endothelial barriers near infection sites within minutes after injection and accumulate close to granulomas...
August 6, 2018: ACS Nano
Elizabeth A García, Federico C Blanco, María M Bigi, Cristina L Vazquez, Marina A Forrellad, Rosana V Rocha, Paul Golby, Marcelo A Soria, Fabiana Bigi
Mycobacterium bovis is the causative agent of bovine tuberculosis and is a member of Mycobacterium tuberculosis complex, which causes tuberculosis in a number of mammals including humans. Previous studies have shown that the genes encoding the two-component system PhoPR, which regulates several genes involved in the virulence of M. tuberculosis, are polymorphic in M. bovis, when compared to M. tuberculosis, which results in a dysfunctional two-component system. In this study we investigated the role of PhoPR in two M...
August 2018: Veterinary Microbiology
Ahmad Qasem, Saleh A Naser
Background The role of Mycobacteriumavium subspecies paratuberculosis (MAP) in Crohn's disease (CD) is increasingly accepted as evident by detection of the bacteria in the blood and intestinal tissue from patients with CD, and by supporting data from several open-label anti-MAP treatment studies. Tumour necrosis factor alpha (TNFα) monoclonal antibodies (anti-TNFα) have been widely used for CD treatment. Despite the short-term benefit of anti-TNFα in controlling CD symptoms, most patients suffer from detrimental adverse effects, including higher susceptibility to mycobacterial infections...
2018: BMJ Open Gastroenterology
Bineeta Kashyap, Nisha Goyal, N P Singh, Iqbal R Kaur
Pleural tuberculosis accounts for nearly 20% of Extra pulmonary tuberculosis. Adenosine deaminase, commonly used biomarker for the diagnosis, is non specific and there is paucity of literature on its correlation with conventional or newer methods for the diagnosis of extra pulmonary forms of TB. The aim of the study was to assess diagnostic potential of T cell function markers [interferon (IFN-γ), interleukin (IL-2) and IFN-γ/IL-2 ratio]; macrophage activation marker [neopterin]; and oxidative stress markers [protein carbonyl and malondialdehyde (MDA)] in pleural tuberculosis...
July 2018: Indian Journal of Clinical Biochemistry: IJCB
Aneesh Thakur, Athina Andrea, Heidi Mikkelsen, Joshua S Woodworth, Peter Andersen, Gregers Jungersen, Claus Aagaard
There is a need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis and Mycobacterium avium subsp. paratuberculosis in a number of species. One of the main challenges for vaccine development is the lack of safe adjuvants that induce protective immune responses. Cationic Adjuvant Formulation 01 (CAF01)-an adjuvant based on trehalose dibehenate (TDB) and targeting the Mincle receptor-has entered human trials based on promising pre-clinical results in a number of species...
2018: PloS One
Alex Olson, Elizabeth J Ragan, Lydia Nakiyingi, Nina Lin, Karen R Jacobson, Jerrold J Ellner, Yukari C Manabe, Manish Sagar
BACKGROUND: Mycobacterium tuberculosis (TB) infection induces systemic inflammation that could impact HIV-1 persistence. SETTING: HIV-1 seropositive individuals either with or without pulmonary TB disease were recruited in Kampala, Uganda METHODS:: Plasma cytokines, HIV-1 DNA, and cell-associated (ca)-RNA were compared among those co-infected with TB (cases) to those without TB (controls). TB co-infected cases and controls were compared at presentation (n = 15 and n = 16 respectively) and at around 6 months after HIV-1 treatment initiation among those that had achieved virologic suppression (n = 6 and n = 8 respectively)...
July 26, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
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
Feriannys Rivas, Andrea Medeiros, Esteban Rodríguez Arce, Marcelo Comini, Camila M Ribeiro, Fernando R Pavan, Dinorah Gambino
Searching for prospective agents against infectious diseases, four new ferrocenyl derivatives, [M(L)(dppf)4](PF6 ), with M = Pd(II) or Pt(II), dppf = 1,1'-bis(dipheny1phosphino) ferrocene and HL = tropolone (HTrop) or hinokitiol (HHino), were synthesized and characterized. Complexes and ligands were evaluated against the bloodstream form of T. brucei, L. infantum amastigotes, M. tuberculosis (MTB) sensitive strain and MTB clinical isolates. Complexes showed a significant increase of the anti-T. brucei activity with respect to the free ligands (>28- and >46-fold for Trop and 6- and 22-fold for Hino coordinated to Pt-dppf and Pd-dppf, respectively), yielding IC50 values < 5 μM...
October 2018: Journal of Inorganic Biochemistry
Tungadri Bose, Chandrani Das, Anirban Dutta, Vishnuvardhan Mahamkali, Sudipta Sadhu, Sharmila S Mande
BACKGROUND: Mycobacterium tuberculosis infection in humans is often associated with extended period of latency. To adapt to the hostile hypoxic environment inside a macrophage, M. tuberculosis cells undergo several physiological and metabolic changes. Previous studies have mostly focused on inspecting individual facets of this complex process. In order to gain deeper insights into the infection process and to understand the coordination among different regulatory/ metabolic pathways in the pathogen, the current in silico study investigates three aspects, namely, (i) host-pathogen interactions (HPIs) between human and M...
July 27, 2018: BMC Genomics
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