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macrophages tuberculosis

Tae Sung Kim, Yeung Bae Jin, Yi Sak Kim, Sup Kim, Jin Kyung Kim, Hye-Mi Lee, Hyun-Woo Suh, Jin Ho Choe, Young Jae Kim, Bon-Sang Koo, Han-Na Kim, Mingyu Jung, Sang-Hee Lee, Don-Kyu Kim, Chaeuk Chung, Ji-Woong Son, Jung-Joon Min, Jin-Man Kim, Chu-Xia Deng, Hyun Seok Kim, Sang-Rae Lee, Eun-Kyeong Jo
SIRT3 (sirtuin 3), a mitochondrial protein deacetylase, maintains respiratory function, but its role in the regulation of innate immune defense is largely unknown. Herein, we show that SIRT3 coordinates mitochondrial function and macroautophagy/autophagy activation to promote anti-mycobacterial responses through PPARA (peroxisome proliferator activated receptor alpha). SIRT3 deficiency enhanced inflammatory responses and mitochondrial dysfunction, leading to defective host defense and pathological inflammation during mycobacterial infection...
February 17, 2019: Autophagy
Hasan Tükenmez, Isabel Edström, Sadaf Kalsum, Clara Braian, Ramesh Ummanni, Stina Berglund Fick, Charlotta Sundin, Maria Lerm, Mikael Elofsson, Christer Larsson
The effect of corticosteroids on human physiology is complex and their use in tuberculosis patients remains controversial. In a high-throughput screening approach designed to discover virulence inhibitors, several corticosteroids were found to prevent cytolysis of fibroblasts infected with mycobacteria. Further experiments with Mycobacterium tuberculosis showed anti-cytolytic activity in the 10 nM range, but no effect on bacterial growth or survival in the absence of host cells at 20 μM. The results from a panel of corticosteroids with various affinities to the glucocorticoid- and mineralocorticoid receptors indicate that the inhibition of cytolysis most likely is mediated through the glucocorticoid receptor...
February 14, 2019: Biochemical and Biophysical Research Communications
Aryadne L de Almeida, Katiany R Caleffi-Ferracioli, Regiane B de L Scodro, Vanessa P Baldin, Débora C Montaholi, Luiza F Spricigo, Sandra S Nakamura-Vasconcelos, Laíse A Hegeto, Eloísa G Sampiron, Giovana F Costacurta, Diego A Dos S Yamazaki, Gisele de F Gauze, Vera Ld Siqueira, Rosilene F Cardoso
AIM:  To evaluate (i) the in vitro activity of eugenol (EUG) and three derivatives against Mycobacterium tuberculosis (Mtb), nontuberculous mycobacteria (NTM) and other bacteria, (ii) the EUG and antituberculosis drugs combinatory effect and (iii) the EUG and its derivatives cytotoxicity. MATERIALS & METHODS:  Minimum inhibitory concentration of the compounds were determined by resazurin microtiter or broth microdilution assay and the drug interaction between EUG and antituberculosis drugs by resazurin drug combination microtiter...
February 13, 2019: Future Microbiology
Kristin N Adams, Amit Kumar Verma, Radha Gopalaswamy, Harresh Adikesavalu, Dinesh Kumar Singhal, Srikanth Tripathy, Uma Devi Ranganathan, David R Sherman, Kevin B Urdahl, Lalita Ramakrishnan, Rafael E Hernandez
The Mycobacterium tuberculosis lineage 4 strains CDC1551 and H37Rv develop tolerance to multiple antibiotics upon macrophage residence. To determine whether macrophage-induced tolerance is a general feature of clinical M. tuberculosis isolates, we assessed macrophage-induced drug tolerance in strains from lineages 1-3, representing the other predominant M. tuberculosis strains responsible for tuberculosis globally. All 3 lineages developed isoniazid tolerance. While lineage 1, 3, and 4 strains developed rifampin tolerance, lineage 2 Beijing strains did not...
February 7, 2019: Journal of Infectious Diseases
Jia-Hui Deng, Han-Yu Chen, Chun Huang, Jia-Min Yan, Zhinan Yin, Xiao-Lian Zhang, Qin Pan
Macrophages are the primary host target cells of Mycobacterium tuberculosis (M. tb). As a subunit of immunoregulatory cytokines IL-27 and IL-35, Epstein-Barr virus-induced gene 3 (EBI3) has typically been explored as the secreted form and assessed in terms of its effects triggered by extracellular EBI3. However, little is known about intracellular EBI3 function. In the current study, we report that EBI3 production by macrophages is elevated in TB patients. We further demonstrate that increased EBI3 accumulates in virulent M...
February 11, 2019: Pathogens and Disease
Kee Woong Kwon, So Jeong Kim, Hongmin Kim, Woo Sik Kim, Soon Myung Kang, Eunsol Choi, Sang-Jun Ha, Joo-Heon Yoon, Sung Jae Shin
Recently, interest in IL-15-differentiated cells has increased; however, the phenotypic definition of IL-15-differentiated bone marrow-derived cells (IL-15-DBMCs) is still under debate, particularly the generation of IFN-γ-producing innate cells such as premature NK (pre-mNK) cells, natural killer dendritic cells (NKDCs), interferon-producing killer dendritic cells (IKDCs), and type 1 innate lymphoid cells (ILC1s), all of which are IL-15-dependent. Here, we revisited the immunophenotypic characteristics of IFN-γ-producing IL-15-DBMCs and their functional role in the control of intracellular Mycobacterium tuberculosis (Mtb) infection...
2019: International Journal of Biological Sciences
Xin-Xin Liu, Wei-Bing Liu, Meng-Jia Shen, Bang-Ce Ye
Mycobacterium tuberculosis utilizes fatty acids of the host as the carbon source. Metabolism of odd chain fatty acids by Mycobacterium tuberculosis produces propionyl-CoA. Methylcitrate cycle is essential for Mycobacteria to utilize the propionyl-CoA to persist and grow on these fatty acids. In M. smegmatis , methylcitrate synthase, methylcitrate dehydratase, and methylisocitrate lyase involved in methylcitrate cycle are encoded by prpC, prpD, and prpB, respectively, in operon prpDBC In this study, we found that the nitrogen regulator GlnR directly binds to the promoter region of prpDBC operon and inhibits its transcription...
February 11, 2019: Journal of Bacteriology
Evgeniya V Nazarova, Christine R Montague, Lu Huang, Thuy La, David Russell, Brian C VanderVen
Mycobacterium tuberculosis (Mtb) imports and metabolizes fatty acids to maintain infection within human macrophages. Although this is a well-established paradigm, the bacterial factors required for fatty acid import are poorly understood. Previously, we found that LucA and Mce1 are required for fatty acid import in Mtb (Nazarova et al., 2017). Here, we identified additional Mtb mutants that have a reduced ability to import a fluorescent fatty acid substrate during infection within macrophages. This screen identified the novel genes as rv2799 and rv0966c as be necessary for fatty acid import and confirmed the central role for Rv3723/LucA and putative components of the Mce1 fatty acid transporter (Rv0200/OmamB, Rv0172/Mce1D, and Rv0655/MceG) in this process...
February 8, 2019: ELife
Vanesa Andreu, Ane Larrea, Pablo Rodriguez-Fernandez, Salvador Alfaro, Begoña Gracia, Ainhoa Lucía, Laura Usón, Andromeda-Celeste Gomez, Gracia Mendoza, Alicia Lacoma, Jose Dominguez, Cristina Prat, Victor Sebastian, José Antonio Ainsa, Manuel Arruebo
AIM: Production of Matryoshka-type gastroresistant microparticles containing antibiotic-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (NP) against Mycobacterium tuberculosis. MATERIALS & METHODS: The emulsification and evaporation methods were followed for the synthesis of PLGA-NPs and methacrylic acid-ethyl acrylate-based coatings to protect rifampicin from degradation under simulated gastric conditions. RESULTS & CONCLUSION: The inner antibiotic-loaded NPs here reported can be released under simulated intestinal conditions whereas their coating protects them from degradation under simulated gastric conditions...
February 8, 2019: Nanomedicine
Tomislava Skuhala, Anita Atelj, Jelena Prepolec, Mahmoud Al-Mufleh, Andrija Stanimirović, Dalibor Vukelić
BACKGROUND: Tumor necrosis factor-α (TNF-α) antagonists, most of which are monoclonal antibodies, became a widespread treatment for autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel diseases, psoriasis, psoriatic arthritis, hidradenitis suppurativa and uveitis. Their use is based on the blockage of TNF-α, which plays an important role in granulomas formation, development of phagosomes, activation and differentiation of macrophages, immune response against viral pathogens...
February 7, 2019: BMC Infectious Diseases
Xinying Zhou, Jiahui Yang, Zelin Zhang, Lijie Zhang, Bo Zhu, Linmiao Lie, Yubin Huang, Rui Ma, Chaoying Zhou, Shengfeng Hu, Qian Wen, Li Ma
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) represents one of the greatest threats to human health., Interferons (IFNs) in combination with the first-line of anti-TB drugs have been used for treating TB for decades in the clinic, but how Mtb infection regulates interferon-stimulated genes (ISGs) in human macrophages (Mϕs) remains unknown. In this study, we investigated the expression-signature and associated innate signaling mechanisms of ISGs in Mtb-infected human monocyte-derived Mϕs (hMDMs) and THP-1-derived Mϕs (THP-1-Mϕs)...
February 3, 2019: International Journal of Molecular Sciences
Nathan J MacGilvary, Yuzo L Kevorkian, Shumin Tan
Successful host colonization by bacteria requires sensing and response to the local ionic milieu, and coordination of responses with the maintenance of ionic homeostasis in the face of changing conditions. We previously discovered that Mycobacterium tuberculosis (Mtb) responds synergistically to chloride (Cl-) and pH, as cues to the immune status of its host. This raised the intriguing concept of abundant ions as important environmental signals, and we have now uncovered potassium (K+) as an ion that can significantly impact colonization by Mtb...
February 4, 2019: PLoS Pathogens
Elena Ufimtseva, Natalya Eremeeva, Sergey Bayborodin, Tatiana Umpeleva, Diana Vakhrusheva, Sergey Skornyakov
Tuberculosis (TB) is a dangerous airborne disease caused by Mycobacterium tuberculosis (Mtb) and characterized by a tight interplay between pathogen and host cells, mainly alveolar macrophages. Studies of the mechanisms of Mtb survival within human cells during TB disease are extremely important for the development of new strategies and drugs for TB treatment. We have used the ex vivo cultures of alveolar macrophages and histological sections obtained from the resected lungs of patients with pulmonary TB to establish the unique features of Mtb lifestyle in host cells...
January 2019: Tuberculosis
Erik Nieto-Patlán, Jeanet Serafín-López, Isabel Wong-Baeza, Sonia M Pérez-Tapia, Laura Cobos-Marín, Sergio Estrada-Parra, Iris Estrada-García, Alma D Chávez-Blanco, Rommel Chacón-Salinas
Tuberculosis is one of the leading causes of mortality worldwide, it is caused by Mycobacterium tuberculosis (Mtb), a bacteria that employs several strategies to evade the host immune response. For instance, Mtb interferes with the overexpression of class II transactivator (CIITA) in macrophages exposed to IFN-γ by inhibiting histone acetylation at its promoter, which can be reverted by the histone deacetylase inhibitor (HDACi) sodium butyrate. In this work, we evaluated whether a different HDACi, valproic acid (VPA), could revert the inhibition of gene expression induced by Mtb...
January 2019: Tuberculosis
Shannon M Lange, Melanie C McKell, Stephanie M Schmidt, Junfang Zhao, Rebecca R Crowther, Lisa C Green, Rebecca L Bricker, Eusondia Arnett, S Eleonore Köhler, Larry S Schlesinger, Kenneth D R Setchell, Joseph E Qualls
Immunonutrition as a therapeutic approach is rapidly gaining interest in the fight against infection. Targeting l-arginine metabolism is intriguing, considering this amino acid is the substrate for antimicrobial NO production by macrophages. The importance of l-arginine during infection is supported by the finding that inhibiting its synthesis from its precursor l-citrulline blunts host defense. During the first few weeks following pulmonary mycobacterial infection, we found a drastic increase in l-citrulline in the lung, even though serum concentrations were unaltered...
February 1, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Srabasti Sengupta, Saba Naz, Ishani Das, Abdul Ahad, Avinash Padhi, Sumanta Kumar Naik, Geetanjali Ganguli, Kali Prasad Pattanaik, Sunil Kumar Raghav, Vinay Kumar Nandicoori, Avinash Sonawane
No abstract text is available yet for this article.
February 1, 2019: Journal of Biological Chemistry
Keertan Dheda, Laura Lenders, Shashikant Srivastava, Gesham Magombedze, Helen Wainwright, Prithvi Raj, Stephen J Bush, Gabriele Pollara, Rachelle Steyn, Malika Davids, Anil Pooran, Timothy Pennel, Anthony Linegar, Ruth McNerney, Loven Moodley, Jotam G Pasipanodya, Carolin T Turner, Mahdad Noursadeghi, Robin M Warren, Edward Wakeland, Tawanda Gumbo
RATIONALE: There is poor understanding about protective immunity and the pathogenesis of cavitation in tuberculosis patients. OBJECTIVES: To map pathophysiological pathways at anatomically distinct positions within the human tuberculosis cavity. METHODS: Biopsies were obtained from eight pre-determined locations within lung cavities of multidrug-resistant tuberculosis patients undergoing therapeutic surgical resection (n=14) and healthy lung tissue from non-tuberculosis controls (n=10)...
January 29, 2019: American Journal of Respiratory and Critical Care Medicine
Molly A Matty, Daphne R Knudsen, Eric M Walton, Rebecca W Beerman, Mark R Cronan, Charlie J Pyle, Rafael E Hernandez, David M Tobin
Mycobacterium tuberculosis is the leading worldwide cause of death due to a single infectious agent. Existing anti-tuberculous therapies require long treatments and are complicated by multi-drug-resistant strains. Host-directed therapies have been proposed as an orthogonal approach, but few have moved into clinical trials. Here, we use the zebrafish- Mycobacterium marinum infection model as a whole-animal screening platform to identify FDA-approved, host-directed compounds. We identify multiple compounds that modulate host immunity to limit mycobacterial disease, including the inexpensive, safe, and widely used drug clemastine...
January 29, 2019: ELife
Pritsana Sawutdeechaikul, Felipe Cia, Gregory J Bancroft, Supason Wanichwecharungruang, Chutamath Sittplangkoon, Tanapat Palaga
Subunit vaccine is safe and more stable than live vaccine but it has disadvantage in eliciting poor immune response. To develop a subunit vaccine, an effective delivery system targeting the key elements of the protective immune response is a prerequisite. In this study, oxidized carbon nanosphere (OCN) was used as a subunit vaccine delivery system and tuberculosis (TB) was chosen as a model disease. TB is among the deadliest infectious diseases worldwide and an effective vaccine is urgently needed. The ability of OCN to deliver recombinant Mycobacterium tuberculosis (Mtb) proteins, Ag85B and HspX, into bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs) were investigated...
January 29, 2019: Journal of Microbiology and Biotechnology
Giuseppe Tripodo, Sara Perteghella, Pietro Grisoli, Adriana Trapani, Maria Luisa Torre, Delia Mandracchia
This work aims at designing a drug delivery system for rifampicin (RIF) to be used for the therapy of infections from mycobacterium tuberculosis or other lung-colonizing bacteria. We are proposing, in particular, the delivery of RIF by micelles based on inulin functionalized with vitamin E (INVITE). We previously demonstrated that INVITE micelles are formed from the self-assembling sustained by the interaction, within the hydrophobic core, of aromatic groups belonging to vitamin E. It points on the effectiveness of these biocompatible systems in incorporating aromatic-group-bearing hydrophobic drug such as RIF...
January 24, 2019: European Journal of Pharmaceutics and Biopharmaceutics
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