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autophagy M.tuberculosis

Kavita Rawat, Swetarka Das, Budai S Vivek Vinod, Umeshkumar Vekariya, Tanu Garg, Arunava Dasgupta, Raj Kamal Tripathi
AIMS: β casein fragment peptide (54-59) downregulates Basic Transcription factor 3a (BTF3a) in macrophages and exhibits enhanced clearance of M. bovis BCG and several other intracellular pathogens. However, the direct effect of BTF3a downregulation on Mycobacterium tuberculosis (Mtb) survival and the probable pathways involved have not yet been studied. Therefore, the present study was undertaken to deduce the antimycobacterial significance of BTF3a in human macrophages. MAIN METHODS: CRISPR/Cas 9 gRNA was designed to downregulate BTF3a in THP1 derived macrophages...
January 23, 2019: Life Sciences
Tarun K Upadhyay, Nida Fatima, Akanksha Sharma, Deepak Sharma, Rolee Sharma
Recently, yeast-derived glucan particles (GP) have emerged as novel drug delivery agents that provide for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors. In our previous study, we prepared GP loaded with high payload (40.5 + 1.9%) of rifabutin (RB) nano-particles [(RB-NPs)-GP]. We investigated the anti-mycobacterial efficacy and cellular activation responses within Mycobacterium tuberculosis (M. tuberculosis) infected J774 macrophage cells following exposure to the (RB-NPs)-GP formulation...
December 2019: Artificial Cells, Nanomedicine, and Biotechnology
Krishnaveni Mohareer, Suman Asalla, Sharmistha Banerjee
Tuberculosis (TB) continues to be the leading cause of death by any single infectious agent, accounting for around 1.7 million annual deaths globally, despite several interventions and support programs by national and international agencies. With the development of drug resistance in Mycobacterium tuberculosis (M. tb), there has been a paradigm shift in TB research towards host-directed therapy. The potential targets include the interactions between host and bacterial proteins that are crucial for pathogenesis...
December 2018: Tuberculosis
Shima Hadifar, Ava Behrouzi, Abolfazl Fateh, Shohreh Khatami, Fatemeh Rahimi Jamnani, Seyed Davar Siadat, Farzam Vaziri
Alveolar epithelial cell (AEC) provides a replication niche for Mycobacterium tuberculosis. Based on the role of AEC in M. tuberculosis pathogenesis and existence of genetic diversity within this bacterium, we investigated interactions between AEC II and two different M. tuberculosis lineages. We have compared the transcriptome and cytokines/chemokines levels of A549 infected by M. tuberculosis lineage three and four using qRT-PCR and ELISA arrays, respectively. We showed different M.  tuberculosis strains induced changes in different effectors that involved in TLRs and NF-κB signaling pathways...
September 7, 2018: Journal of Cellular Physiology
Rokeya Sultana Rekha, Akhirunnesa Mily, Tajnin Sultana, Ahsanul Haq, Sultan Ahmed, S M Mostafa Kamal, Annemarie van Schadewijk, Pieter S Hiemstra, Gudmundur H Gudmundsson, Birgitta Agerberth, Rubhana Raqib
BACKGROUND: We have previously shown that 8 weeks' treatment with phenylbutyrate (PBA) (500mgx2/day) with or without vitamin D3 (vitD3 ) (5000 IU/day) as host-directed therapy (HDT) accelerated clinical recovery, sputum culture conversion and increased expression of cathelicidin LL-37 by immune cells in a randomized, placebo-controlled trial in adults with pulmonary tuberculosis (TB). In this study we further aimed to examine whether HDT with PBA and vitD3 promoted clinically beneficial immunomodulation to improve treatment outcomes in TB patients...
July 4, 2018: BMC Infectious Diseases
Michelle M Coleman, Sharee A Basdeo, Amy M Coleman, Clíona Ní Cheallaigh, Celia Peral de Castro, Anne Marie McLaughlin, Padraic J Dunne, James Harris, Joseph Keane
Vitamin A deficiency strongly predicts the risk of developing tuberculosis (TB) in individuals exposed to Mycobacterium tuberculosis (Mtb). The burden of antibiotic-resistant TB is increasing globally; therefore, there is an urgent need to develop host-directed adjunctive therapies to treat TB. Alveolar macrophages, the niche cell for Mtb, metabolize vitamin A to all-trans retinoic acid (atRA), which influences host immune responses. We sought to determine the mechanistic effects of atRA on the host immune response to intracellular bacterial infection in primary human and murine macrophages...
November 2018: American Journal of Respiratory Cell and Molecular Biology
Anetta Härtlova, Susanne Herbst, Julien Peltier, Angela Rodgers, Orsolya Bilkei-Gorzo, Antony Fearns, Brian D Dill, Heyne Lee, Rowan Flynn, Sally A Cowley, Paul Davies, Patrick A Lewis, Ian G Ganley, Jennifer Martinez, Dario R Alessi, Alastair D Reith, Matthias Trost, Maximiliano G Gutierrez
Mutations in the leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease, chronic inflammation and mycobacterial infections. Although there is evidence supporting the idea that LRRK2 has an immune function, the cellular function of this kinase is still largely unknown. By using genetic, pharmacological and proteomics approaches, we show that LRRK2 kinase activity negatively regulates phagosome maturation via the recruitment of the Class III phosphatidylinositol-3 kinase complex and Rubicon to the phagosome in macrophages...
June 15, 2018: EMBO Journal
Gina Leisching, Ian Wiid, Bienyameen Baker
Evidence to-date points to a detrimental role of the type I IFNs during tuberculosis. The mechanisms underpinning the IFNαβ-mediated exacerbation of the disease is unclear. The 2'-5'-oligoadenylate synthetases (OAS), namely OAS1, OAS2 and OAS3 are part of the interferon-induced genes which until now have been synonymous with an anti-viral function. Blood transcriptome profiling has continuously observed their upregulation in a number of gene expression signatures which discriminate active TB from latent TB infection, however the role of the OASs and the effect that their expression has on the pathogenesis and persistence of TB is unknown...
April 23, 2018: Journal of Infectious Diseases
Min Wan, Xiao Tang, Rokeya Sultana Rekha, S S V Jagadeeswara Rao Muvva, Susanna Brighenti, Birgitta Agerberth, Jesper Z Haeggström
Prostaglandin (PG)E2 is an arachidonic acid-derived lipid mediator that plays an important role in inflammation and immunity. In this study, we demonstrate that PGE2 suppresses basal and 1,25-dihydroxy vitamin D3 (VD3 )-induced expression of hCAP18/LL-37 via E prostanoid (EP)2 and EP4 receptors. In humans, VD3 up-regulates vitamin D receptor (VDR) expression and promotes transcription of the cathelicidin hCAP18/LL-37 gene, whereas PGE2 counteracts this effect. We find that PGE2 induces the cAMP/PKA-signaling pathway and enhances the expression of the inhibitory transcription factor cAMP-responsive modulator/inducible cAMP early repressor, which prevents VDR expression and induction of hCAP18/LL-37 in human macrophages...
May 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Wenjing Xiong, Qian Wen, Xialin Du, Jinli Wang, Wenting He, Ruining Wang, Shengfeng Hu, Xinying Zhou, Jiahui Yang, Yuchi Gao, Li Ma
In Mycobacterium tuberculosis-infected macrophages, cyclooxygenase-2 (COX-2) expression considerably increases to defend the body against mycobacteria by regulating adaptive immunity and restoring the mitochondrial inner membrane. Moreover, in cancer cells, COX-2 enhances the autophagy machinery, an important bactericidal mechanism. However, the association between M. tuberculosis-induced COX-2 and autophagy-mediated antimycobacterial response has not been explored. Here, COX-2 expression silencing reduced the autophagy and bactericidal activity against intracellular M...
March 28, 2018: Journal of Infectious Diseases
Zhan Chen, Xiao-Yi Shao, Chao Wang, Min-Hui Hua, Cheng-Niu Wang, Xin Wang, Qian-Jin Wang, Jin-Yi Yao, Yi-Hui Fan, Yong-Wei Qin
Mycobacterium tuberculosis (M. tuberculosis) invading and activating microglia causes the most serious subtypes of tuberculosis called tubercular meningitis. However, the developmental process of tubercular meningitis, especially the early phase, is poorly understood due to lacking well-established and well-accepted visible models in vitro and in vivo. Here, consistent with one recent report, we found Mycobacterium marinum (M. marinum) invade the zebrafish brain and subsequently cause granuloma-like structures...
February 2018: Journal of Molecular Neuroscience: MN
Stefan Köster, Thais Klevorn, Kadamba Papavinasasundaram, Christopher M Sassetti, Cynthia Portal-Celhay, Jennifer A Philips
Development of a new vaccine against tuberculosis is urgently needed. Recent work has demonstrated that two related LC3-associated trafficking pathways, autophagy and LC3-associated phagocytosis (LAP), enhance antigen presentation and might play a role in vaccine efficacy. Mycobacterium tuberculosis inhibits both LC3-trafficking pathways. Moreover, the vaccine strain, BCG, induces even less LC3-trafficking than M. tuberculosis, which may help explain its limited efficacy. To determine whether enhanced LC3-trafficking can improve efficacy of a live, attenuated M...
February 8, 2018: Vaccine
Marilena P Etna, Alessandro Sinigaglia, Angela Grassi, Elena Giacomini, Alessandra Romagnoli, Manuela Pardini, Martina Severa, Melania Cruciani, Fabiana Rizzo, Eleni Anastasiadou, Barbara Di Camillo, Luisa Barzon, Gian Maria Fimia, Riccardo Manganelli, Eliana M Coccia
Autophagy is a primordial eukaryotic pathway, which provides the immune system with multiple mechanisms for the elimination of invading pathogens including Mycobacterium tuberculosis (Mtb). As a consequence, Mtb has evolved different strategies to hijack the autophagy process. Given the crucial role of human primary dendritic cells (DC) in host immunity control, we characterized Mtb-DC interplay by studying the contribution of cellular microRNAs (miRNAs) in the post-transcriptional regulation of autophagy related genes...
January 2018: PLoS Pathogens
Bindu Singh, Mohd Saqib, Ananya Gupta, Pawan Kumar, Sangeeta Bhaskar
Mycobacterium indicus pranii (MIP) is a potent vaccine candidate against tuberculosis (TB) as it has demonstrated significant protection in animal models of tuberculosis as well as in clinical trials. Higher protective efficacy of MIP against TB as compared to BCG provoked the efforts to gain insight into the molecular mechanisms underlying MIP mediated protection against Mycobacterium tuberculosis (M.tb). Autophagy, initially described as a cell survival mechanism during starvation, also plays a key role in host resistance to M...
2017: PloS One
I Palucci, I Matic, L Falasca, M Minerva, G Maulucci, M De Spirito, E Petruccioli, D Goletti, F Rossin, M Piacentini, G Delogu
BACKGROUND: Mycobacterium tuberculosis (MTB), the aetiological agent of tuberculosis (TB), is capable of interfering with the phagosome maturation pathway, by inhibiting phagosome-lysosome fusion and the autophagic process to ensure survival and replication in macrophages. Thus, it has been proposed that the modulation of autophagy may represent a therapeutic approach to reduce MTB viability by enhancing its clearance. OBJECTIVE: The aim of this study was to investigate whether transglutaminase type 2 (TG2) is involved in the pathogenesis of MTB...
March 2018: Journal of Internal Medicine
Chung-Lung Cho, Ya-Zhe Lee, Chao-Neng Tseng, Joshua Cho, Yuan-Bin Cheng, Kuo-Wei Wang, Han-Jung Chen, Shean-Jaw Chiou, Chia-Hua Chou, Yi-Ren Hong
Pluchea indica (L.) Less. is a perennial plant known for its versatile uses in traditional medicine. Previous findings have shown that the extracts of Pluchea indica possess significant anti-inflammatory, anti-ulcer and anti-tuberculosis activity. The aim of this study was to demonstrate the anticancer activity of the hexane fraction of P. indica root extract (H-PIRE) in human glioblastoma cells using flow cytometric and western blot analysis. The results shoewd that, H-PIRE suppressed the growth of glioblastoma cells in a dose-dependent manner...
November 2017: Biomedical Reports
Manik Retno Wahyunitisari, Ni Made Mertaniasih, Muhammad Amin, Wayan T Artama, Eko B Koendhori
BACKGROUND: Mycobacterium tuberculosis induces cellular necrosis that could promote spread of infection. The aim of this study is to analyze the effects of Vitamin D3 supplementation to improve the effectiveness of 2nd-line anti-tuberculosis (TB) drug therapy, especially in relation with cell death pathways. METHODS: Mus musculus C3HeB/FeJ was randomly divided into four groups containing eight animals each. The 1st group (G1), consisting of mice that were intratracheally infected with multidrug-resistant strain of M...
October 2017: International Journal of Mycobacteriology
Lucy C K Bell, Mahdad Noursadeghi
Co-infection with Mycobacterium tuberculosis is the leading cause of death in individuals infected with HIV-1. It has long been known that HIV-1 infection alters the course of M. tuberculosis infection and substantially increases the risk of active tuberculosis (TB). It has also become clear that TB increases levels of HIV-1 replication, propagation and genetic diversity. Therefore, co-infection provides reciprocal advantages to both pathogens. In this Review, we describe the epidemiological associations between the two pathogens, selected interactions of each pathogen with the host and our current understanding of how they affect the pathogenesis of TB and HIV-1/AIDS in individuals with co-infections...
February 2018: Nature Reviews. Microbiology
Haojun Xie, Chufang Li, Mincong Zhang, Nanshan Zhong, Ling Chen
BACKGROUND: The human immunity-related GTPase M (IRGM) is involved in regulating autophagy against invading pathogens. Recently, inconsistent results have been reported about the association between IRGM polymorphisms and tuberculosis risk in several studies. METHODS: We searched the PubMed, Embase, and Web of Knowledge, and extracted data from eligible articles to estimate the associations between IRGM polymorphisms (rs10065172, rs4958842, rs4859843, rs4859846, and rs72553867) and tuberculosis risk...
October 2017: Medicine (Baltimore)
Arshad Khan, Chinnaswamy Jagannath
Mycobacterium tuberculosis is one of the most deadly human pathogens known today in modern world, responsible for about 1.5 million deaths annually. Development of TB disease occurs only in 1 out of 10 individuals exposed to the pathogen which indicates that the competent host defense mechanisms exist in majority of the hosts to control the infection. In the last decade, autophagy has emerged as a key host immune defense mechanism against intracellular M. tuberculosis infection. Autophagy has been demonstrated not only as an effective antimicrobial mechanism for the clearance of M...
September 3, 2017: International Reviews of Immunology
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