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macrophage tuberculosis

Philipp Stüve, Lucía Minarrieta, Hanna Erdmann, Catharina Arnold-Schrauf, Maxine Swallow, Melanie Guderian, Freyja Krull, Alexandra Hölscher, Peyman Ghorbani, Jochen Behrends, Wolf-Rainer Abraham, Christoph Hölscher, Tim D Sparwasser, Luciana Berod
Mycobacterium tuberculosis ( Mtb ), the causative agent of human tuberculosis, is able to efficiently manipulate the host immune system establishing chronic infection, yet the underlying mechanisms of immune evasion are not fully understood. Evidence suggests that this pathogen interferes with host cell lipid metabolism to ensure its persistence. Fatty acid metabolism is regulated by acetyl-CoA carboxylase (ACC) 1 and 2; both isoforms catalyze the conversion of acetyl-CoA into malonyl-CoA, but have distinct roles...
2018: Frontiers in Immunology
Guanghui Dang, Yingying Cui, Lei Wang, Tiantian Li, Ziyin Cui, Ningning Song, Liping Chen, Hai Pang, Siguo Liu
Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), which mainly causes pulmonary injury and tubercles. Although macrophages are generally considered to harbor the main cells of M. tuberculosis , new evidence suggests that neutrophils are rapidly recruited to the infected lung. M. tuberculosis itself, or its early secreted antigenic target protein 6 (ESAT-6), can induce formation of neutrophil extracellular traps (NETs). However, NETs trap mycobacteria but are unable to kill them. The role of NETs' formation in the pathogenesis of mycobacteria remains unclear...
2018: Frontiers in Immunology
Asma Ahmed, Komal Dolasia, Sangita Mukhopadhyay
Mycobacterium tuberculosis PPE18 is a member of the PPE family. Previous studies have shown that recombinant PPE18 (rPPE18) protein binds to TLR2 and triggers a signaling cascade which reduces levels of TNF-α and IL-12, and increases IL-10 in macrophages. Because TNF-α is a major mediator of the pathophysiology of sepsis and blocking inflammation is a possible line of therapy in such circumstances, we tested the efficacy of rPPE18 in reducing symptoms of sepsis in a mouse model of Escherichia coli- induced septic peritonitis...
April 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Kata Horváti, Gergo Gyulai, Antal Csámpai, János Rohonczy, Eva Kiss, Szilvia Erika Bosze
Nanoparticles consist of biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) are promising carriers for drug molecules to improve the treatment of tuberculosis. Surface modifiers, such as Pluronic F127, are essential for biocompatibility and for the protection against particle aggregation. This study demonstrates a successful approach to conjugate Pluronic F127 coated PLGA nanoparticles with Tuftsin, which has been reported as a macrophage-targeting peptide. Transformation of Pluronic F127 hydroxyl groups - which have limited reactivity - into aldehyde groups provide a convenient way to bind aminooxy-peptide derivatives in one step reaction...
April 18, 2018: Bioconjugate Chemistry
Huiqing Zheng, John T Williams, Garry B Coulson, Elizabeth R Haiderer, Robert B Abramovitch
Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb), is a deadly disease that requires a long course of treatment. The emergence of drug resistant strains has driven efforts to discover new small molecules that can kill the bacterium. Here we report characterizations of the compound HC2091 that kills Mtb in a time- and dose-dependent manner in vitro , as well as inhibiting Mtb growth in macrophages. Whole genome sequencing of spontaneous resistant mutants to HC2091 identified single nucleotide variants in the mmpL3 mycolic acid transporter gene...
April 16, 2018: Antimicrobial Agents and Chemotherapy
Shuxin Liang, Zhigang Song, Yongyan Wu, Yuanpeng Gao, Mingqing Gao, Fayang Liu, Fengyu Wang, Yong Zhang
Mycobacterium tuberculosis poses a significant global health threat. MicroRNAs play an important role in regulating host anti-mycobacterial defense; however, their role in apoptosis-mediated mycobacterial elimination and inflammatory response remains unclear. In this study, we explored the role of microRNA-27b (miR-27b) in murine macrophage responses to M. tuberculosis infection. We uncovered that the TLR-2/MyD88/NF-κB signaling pathway induced the expression of miR-27b and miR-27b suppressed the production of proinflammatory factors and the activity of NF-κB, thereby avoiding an excessive inflammation during M...
April 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
A V Chechushkov, P M Kozhin, N S Zaitseva, P I Gainutdinov, E B Men'shchikova, A V Troitskii, V A Shkurupy
We studied differences in the production of pro- and anti-inflammatory cytokines and IRF3 transcription factor by peritoneal macrophages from mice of opposite strains CBA/J and C57Bl/6 and the effect of 60-kDa oxidized dextran on these parameters. Macrophages from C57Bl/6 mice were mainly characterized by the production of proinflammatory cytokines TNFα, IL-12, and MCP-1 (markers of M1 polarization). By contrast, CBA/J mice exhibited a relatively high level of anti-inflammatory cytokine IL-10 and lower expression of proinflammatory cytokines (M2 phenotype)...
April 16, 2018: Bulletin of Experimental Biology and Medicine
Hannah J Metcalfe, Lucia Biffar, Sabine Steinbach, Efrain Guzman, Tim Connelley, Ivan Morrison, H Martin Vordermeier, Bernardo Villarreal-Ramos
There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4+ T cells post-boosting. Here, the capacity of Ag85A-specific CD4+ T cell lines - derived before and after viral boosting - to interact with BCG-infected macrophages was evaluated...
April 11, 2018: Vaccine
Mary Lilian Carabali-Isajar, Marisol Ocampo, Deisy Carolina Rodriguez, Magnolia Vanegas, Hernando Curtidor, Manuel Alfonso Patarroyo, Manuel Elkin Patarroyo
Mycobacterium tuberculosis is considered one of the most successful pathogens in the history of mankind, having caused 1.7 million deaths in 2016. The amount of resistant and extensively resistant strains has increased; BCG has been the only vaccine to be produced in more than 100 years though it is still unable to prevent the disease's most disseminated form in adults; pulmonary tuberculosis. The search is thus still on-going for candidate antigens for an antituberculosis vaccine. This paper reports the use of a logical and rational methodology for finding such antigens, this time as peptides derived from the Rv3587c membrane protein...
April 4, 2018: Bioorganic & Medicinal Chemistry
Claudio Counoupas, Rachel Pinto, Gayathri Nagalingam, Warwick J Britton, James A Triccas
Tuberculosis (TB) remains a major cause of mortality and morbidity worldwide, yet current control strategies, including the existing BCG vaccine, have had little impact on disease control. CysVac2, a fusion protein comprising stage-specific Mycobacterium tuberculosis antigens, provided superior protective efficacy against chronic M. tuberculosis infection in mice, compared to BCG. To determine if the delivery of CysVac2 in the context of BCG could improve BCG-induced immunity and protection, we generated a recombinant strain of BCG overexpressing CysVac2 (rBCG:CysVac2)...
April 4, 2018: Vaccine
Catherine A Foss, Julian Sanchez-Bautista, Sanjay K Jain
Macrophages belong to the mononuclear phagocyte system comprising closely related cells of bone marrow origin. Activated macrophages are critical in several diseases such as tuberculosis, sarcoidosis, Crohn's disease, and atherosclerosis. Noninvasive imaging techniques that can specifically image activated macrophages could therefore help in differentiating various forms of inflammatory diseases and to monitor therapeutic responses.
May 2018: Seminars in Nuclear Medicine
Rina La Distia Nora, Kimberley V Walburg, P Martin van Hagen, Sigrid M A Swagemakers, Peter J van der Spek, Edwin Quinten, Mirjam van Velthoven, Tom H M Ottenhoff, Willem A Dik, Mariëlle C Haks
Purpose: Mycobacterium tuberculosis (Mtb) bacilli have been found in retinal pigment epithelial (RPE) cells from uveitis patients without signs of systemic tuberculosis (TB) infection. RPE cells are important for ocular immune privilege and uveitis development. Methods: To address a potential role for Mtb-infected RPE cells in the development of uveitis, we delineated the response to Mtb infection in human RPE cells and primary human macrophages, the main target cell of Mtb...
March 1, 2018: Investigative Ophthalmology & Visual Science
Landon W Locke, Shankaran Kothandaraman, Michael Tweedle, Sarah Chaney, Daniel J Wozniak, Larry S Schlesinger
Granulomas are the histopathologic hallmark of tuberculosis (TB), both in latency and active disease. Diagnostic and therapeutic strategies that specifically target granulomas have not been developed. Our objective is to develop a probe for imaging relevant immune cell populations infiltrating the granuloma. We report the binding specificity of Cyanine 3 (Cy3)-labeled cFLFLFK-PEG12 to human leukocytes and cellular constituents within a human in vitro granuloma model. We also report use of the probe in in vivo studies using a mouse model of lung granulomatous inflammation...
January 2018: Tuberculosis
Mayumi Mori, Ravindra Mode, Jean Pieters
Microbes have interacted with eukaryotic cells for as long as they have been co-existing. While many of these interactions are beneficial for both the microbe as well as the eukaryotic cell, several microbes have evolved into pathogenic species. For some of these pathogens, host cell invasion results in irreparable damage and thus host cell destruction, whereas others use the host to avoid immune detection and elimination. One of the latter pathogens is Mycobacterium tuberculosis , arguably one of the most notorious pathogens on earth...
2018: Frontiers in Cellular and Infection Microbiology
Desi Indriarini, Andriansjah Rukmana, Andi Yasmon
Background: Tuberculosis remains the leading cause of death in the world, especially wherever poverty, malnutrition and poor housing prevail. Mycobacterium tuberculosis Beijing strain is the most common strain that causes tuberculosis in Indonesia. The wide spread of tuberculosis has been further aggravated by HIV-AIDS and drug resistance. Unfortunately, Bacille Calmette-Guerin (BCG) as the current vaccine has different protection function and efficacy. According to function analysis, mce1A gene was predicted to have a role in host invasion and survival of Mycobacterium tuberculosis in human macrophages...
2018: African Journal of Infectious Diseases
Pedro Ferrari Dalberto, Valnês Rodrigues-Junior, Virginia Carla Almeida Falcão, Antônio Frederico Michel Pinto, Bruno Lopes Abbadi, Cristiano Valim Bizarro, Luiz Augusto Basso, Anne Drumond Villela, Diógenes Santiago Santos
Purine nucleoside phosphorylase from Mycobacterium tuberculosis (MtPNP), encoded by deoD gene (Rv3307), is an enzyme from the purine salvage pathway, which has been widely studied as a molecular target for the development of inhibitors with potential antimycobacterial activity. However, the role of MtPNP in tuberculosis pathogenesis and dormancy is still unknown. The present work aims to construct a deoD knockout strain from M. tuberculosis, to evaluate the role of MtPNP in the growth of M. tuberculosis under oxygenated condition and in a dormancy model, and to assess whether deoD gene is important for M...
March 30, 2018: Microbial Pathogenesis
Matshawandile Tukulula, Luis Gouveia, Paulo Paixao, Rose Hayeshi, Brendon Naicker, Admire Dube
PURPOSE: Mycobacterium tuberculosis which causes tuberculosis, is primarily resident within macrophages. 1,3-β-glucan has been proposed as a ligand to target drug loaded nanoparticles (NPs) to macrophages. In this study we characterized the intracellular pharmacokinetics of the anti-tubercular drug rifampicin delivered by 1,3-β-glucan functionalized PLGA NPs (Glu-PLGA). We hypothesized that Glu-PLGA NPs would be taken up at a faster rate than PLGA NPs, and consequently deliver higher amounts of rifampicin into the macrophages...
March 29, 2018: Pharmaceutical Research
Melanie Genoula, José Luis Marín Franco, Maeva Dupont, Denise Kviatcovsky, Ayelén Milillo, Pablo Schierloh, Eduardo Jose Moraña, Susana Poggi, Domingo Palmero, Dulce Mata-Espinosa, Erika González-Domínguez, Juan Carlos León Contreras, Paula Barrionuevo, Bárbara Rearte, Marlina Olyissa Córdoba Moreno, Adriana Fontanals, Agostina Crotta Asis, Gabriela Gago, Céline Cougoule, Olivier Neyrolles, Isabelle Maridonneau-Parini, Carmen Sánchez-Torres, Rogelio Hernández-Pando, Christel Vérollet, Geanncarlo Lugo-Villarino, María Del Carmen Sasiain, Luciana Balboa
The ability of Mycobacterium tuberculosis (Mtb) to persist in its human host relies on numerous immune evasion strategies, such as the deregulation of the lipid metabolism leading to the formation of foamy macrophages (FM). Yet, the specific host factors leading to the foamy phenotype of Mtb-infected macrophages remain unknown. Herein, we aimed to address whether host cytokines contribute to FM formation in the context of Mtb infection. Our approach is based on the use of an acellular fraction of tuberculous pleural effusions (TB-PE) as a physiological source of local factors released during Mtb infection...
2018: Frontiers in Immunology
Minjeong Woo, Connor Wood, Doyoon Kwon, Kyu-Ho Paul Park, György Fejer, Vincent Delorme
Lung alveolar macrophages (AMs) are in the first line of immune defense against respiratory pathogens and play key roles in the pathogenesis of Mycobacterium tuberculosis ( Mtb ) in humans. Nevertheless, AMs are available only in limited amounts for in vitro studies, which hamper the detailed molecular understanding of host- Mtb interactions in these macrophages. The recent establishment of the self-renewing and primary Max Planck Institute (MPI) cells, functionally very close to lung AMs, opens unique opportunities for in vitro studies of host-pathogen interactions in respiratory diseases...
2018: Frontiers in Immunology
Xavier Michelet, Amit Tuli, Huixian Gan, Carolina Geadas, Mahak Sharma, Heinz G Remold, Michael B Brenner
Mycobacterium tuberculosis is an extremely successful pathogen, and its success is widely attributed to its ability to manipulate the intracellular environment of macrophages. A central phenomenon of tuberculosis pathology enabling immune evasion is the capacity of virulent M. tuberculosis (H37Rv) to induce macrophage necrosis, which facilitates the escape of the mycobacteria from the macrophage and spread of infection. In contrast, avirulent M. tuberculosis (H37Ra) induces macrophage apoptosis, which permits Ag presentation and activation of adaptive immunity...
March 28, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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