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Mycobacterium macrophages

Swati Jaiswal, Kishore K Srivastava
Mycobacterium tuberculosis (MTB) is a successful pathogen which increases persistence inside the host macrophage by subverting its defence mechanism. Mycobacteria regulate the pathogenesis and intracellular survival by controlling its interaction with host protein(s). Galectin 3 is a member of the β-galactoside binding gene family which is involved in several biological functions. In the present study we have expressed the mycobacterial protein tyrosine kinase (PtkA) in the cytosol of host macrophages through a eukaryotic promoter vector and found that it down-regulates Galectin 3...
March 12, 2018: Biochemical and Biophysical Research Communications
Denise C Hsu, Kimberly F Breglio, Luxin Pei, Chun-Shu Wong, Bruno B Andrade, Virginia Sheikh, Margery Smelkinson, Constantinos Petrovas, Adam Rupert, Leonardo Gil-Santana, Adrian Zelazny, Steven M Holland, Kenneth Olivier, Daniel Barber, Irini Sereti
Background: Immune reconstitution inflammatory syndrome (IRIS) is an aberrant inflammatory response in individuals with advanced human immunodeficiency virus (HIV) infection, after antiretroviral therapy (ART) initiation. The pathogenesis of Mycobacterium avium complex (MAC)-associated IRIS has not been fully elucidated. Methods: We investigated monocyte and CD4+ T-cell responses in vitro, tumor necrosis factor (TNF) expression in tissues, and plasma cytokines and inflammatory markers, in 13 HIV-infected patients with MAC-IRIS and 14 HIV-uninfected patients with pulmonary MAC infection...
March 10, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Wenting He, Shengfeng Hu, Xialin Du, Qian Wen, Xiao-Ping Zhong, Xinying Zhou, Chaoying Zhou, Wenjing Xiong, Yuchi Gao, Shimeng Zhang, Ruining Wang, Jiahui Yang, Li Ma
The mechanisms by which vitamins regulate immunity and their effect as an adjuvant treatment for tuberculosis have gradually become very important research topics. Studies have found that vitamin B5 (VB5) can promote epithelial cells to express inflammatory cytokines. We aimed to examine the proinflammatory and antibacterial effect of VB5 in macrophages infected with Mycobacterium tuberculosis (MTB) strain H37Rv and the therapeutic potential of VB5 in vivo with tuberculosis. We investigated the activation of inflammatory signal molecules (NF-κB, AKT, JNK, ERK, and p38), the expression of two primary inflammatory cytokines (tumor necrosis factor and interleukin-6) and the bacterial burdens in H37Rv-infected macrophages stimulated with VB5 to explore the effect of VB5 on the inflammatory and antibacterial responses of macrophages...
2018: Frontiers in Immunology
Debika Datta, Preeti Khatri, Ambika Singh, Dhira Rani Saha, Gaurav Verma, Rajagopal Raman, Shibnath Mazumder
Mycobacterium fortuitum is a natural fish pathogen. It induces apoptosis in headkidney macrophages (HKM) of catfish, Clarias sp though the mechanism remains largely unknown. We observed M. fortuitum triggers calcium (Ca2+ ) insult in the sub-cellular compartments which elicits pro-apototic ER-stress factor CHOP. Alleviating ER-stress inhibited CHOP and attenuated HKM apoptosis implicating ER-stress in the pathogenesis of M. fortuitum . ER-stress promoted calpain activation and silencing the protease inhibited caspase-12 activation...
December 2018: Cell Death Discovery
Smriti Srivastava, Devla Bimal, Kapil Bohra, Balram Singh, Prija Ponnan, Ruchi Jain, Mandira Varma-Basil, Jyotirmoy Maity, M Thirumal, Ashok K Prasad
A series of β-d-ribofuranosyl coumarinyl-1,2,3-triazoles have been synthesized by Cu-catalyzed cycloaddition reaction between azidosugar and 7-O-/7-alkynylated coumarins in 62-70% overall yields. The in vitro antimycobacterial activity evaluation of the synthesized triazolo-conjugates against Mycobacterium tuberculosis revealed that compounds were bactericidal in nature and some of them were found to be more active than one of the first line antimycobacterial drug ethambutol against sensitive reference strain H37Rv, and 7 to 420 times more active than all four first line antimycobacterial drugs (isoniazid, rifampicin, ethambutol and streptomycin) against multidrug resistant clinical isolate 591...
February 27, 2018: European Journal of Medicinal Chemistry
Gopinath Viswanathan, Md Jafurulla, G Aditya Kumar, Tirumalai R Raghunand, Amitabha Chattopadhyay
Mycobacteria are intracellular pathogens that can invade and survive within host macrophages. Mycobacterial infections remain a major cause of mortality and morbidity worldwide, with serious concerns of emergence of multi and extensively drug-resistant tuberculosis. While significant advances have been made in identifying mycobacterial virulence determinants, the detailed molecular mechanism of internalization of mycobacteria into host cells remains poorly understood. Although several studies have highlighted the crucial role of sphingolipids in mycobacterial growth, persistence and establishment of infection, the role of sphingolipids in the entry of mycobacteria into host cells is not known...
March 8, 2018: Chemistry and Physics of Lipids
Ruth Bowness, Mark A J Chaplain, Gibin G Powathil, Stephen H Gillespie
If improvements are to be made in tuberculosis (TB) treatment, an increased understanding of disease in the lung is needed. Studies have shown that bacteria in a less metabolically active state, associated with the presence of lipid bodies, are less susceptible to antibiotics, and recent results have highlighted the disparity in concentration of different compounds into lesions. Treatment success therefore depends critically on the responses of the individual bacteria that constitute the infection. We propose a hybrid, individual-based approach that analyses spatio-temporal dynamics at the cellular level, linking the behaviour of individual bacteria and host cells with the macroscopic behaviour of the microenvironment...
March 7, 2018: Journal of Theoretical Biology
Aaron Korkegian, Theresa O'Malley, Yi Xia, Yasheen Zhou, David S Carter, Bjorn Sunde, Lindsay Flint, Dean Thompson, Thomas R Ioerger, Jim Sacchettini, M R K Alley, Tanya Parish
We identified a series of novel 7-phenyl benzoxaborole compounds with activity against Mycobacterium tuberculosis. Compounds had a range of activity with inhibitory concentrations (IC90 ) as low as 5.1 μM and no cytotoxicity against eukaryotic cells (IC50  > 50 μM). Compounds were active against intracellular mycobacteria cultured in THP-1 macrophages. We isolated and characterized resistant mutants with mutations in NADH dehydrogenase (Ndh) or the regulatory protein Mce3R. Mutations suggest that Ndh may be the target of this series...
January 2018: Tuberculosis
Rajendra Kumar Angara, Suhail Yousuf, Shailesh Kumar Gupta, Akash Ranjan
leuCD operon encodes isopropylmalate isomerase (IPMI), an essential enzyme in leucine biosynthesis. Leucine biosynthesis is one of the essential metabolic pathways for Mycobacterium tuberculosis survival inside the macrophage. In this study, we identified an IclR like transcription regulator, Rv2989 involved in regulation of leuCD expression. Further, we have shown that the Rv2989 binding site overlaps with the promoter region of leuCD, indicating its direct involvement in the regulation of this operon. Ectopic expression of Rv2989 in M...
January 2018: Tuberculosis
Xiaolei Wang, Yanhua Wu, Jin Jiao, Qing Huang
Mycobacterium tuberculosis (MTB) infection is a significant contributor to dysregulated T cell-mediated immune response. Here we aimed to evaluate the mechanism of MTB infection in promoting interleukin-10 (IL-10) upregulation. The IL-10 levels in MTB infected THP-1 cells were evaluated with enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR). In challenged THP-1 cells, the HDAC6 and HDAC11 mRNA and protein levels were monitored at varied duration after MTB infection. Further, chromatin immunoprecipitation (ChIP) analysis was used to investigate the interaction between IL-10 expression and HDAC6 or HDAC11...
January 2018: Tuberculosis
Sally A F El-Sahrigy, Azza M O Abdel Rahman, Dalia Y Samaha, Nesrine A Mohamed, Sally M Saber, Hala A Talkhan, Ghada A Ismail, Essam M Ibraheem, Emad M Riad
INTRODUCTION: Tuberculosis (TB) remains a huge worldwide burden, despite extensive vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is inadequate to protect the human population against TB. This underscore the critical necessitate to develop an improved TB vaccine, based on a better understanding of host-pathogen interactions and immune responses during mycobacterial infection. AIM OF THE WORK: To examine whether the exogenous addition of IFN-β could improve dendritic cell (DC) response to Mycobacterium bovis (M...
March 6, 2018: Journal of Immunological Methods
Violeta D Alvarez-Jiménez, Kahiry Leyva-Paredes, Mariano García-Martínez, Luis Vázquez-Flores, Víctor Gabriel García-Paredes, Marcia Campillo-Navarro, Israel Romo-Cruz, Víctor Hugo Rosales-García, Jessica Castañeda-Casimiro, Sirenia González-Pozos, José Manuel Hernández, Carlos Wong-Baeza, Blanca Estela García-Pérez, Vianney Ortiz-Navarrete, Sergio Estrada-Parra, Jeanet Serafín-López, Isabel Wong-Baeza, Rommel Chacón-Salinas, Iris Estrada-García
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb). In the lungs, macrophages and neutrophils are the first immune cells that have contact with the infecting mycobacteria. Neutrophils are phagocytic cells that kill microorganisms through several mechanisms, which include the lytic enzymes and antimicrobial peptides that are found in their lysosomes, and the production of reactive oxygen species. Neutrophils also release extracellular vesicles (EVs) (100-1,000 nm in diameter) to the extracellular milieu; these EVs consist of a lipid bilayer surrounding a hydrophilic core and participate in intercellular communication...
2018: Frontiers in Immunology
Laura Rindi, Nicoletta Lari, Carlo Garzelli
Background: Mycobacterium avium subsp. hominissuis (MAH) is an environmental opportunistic pathogen for humans and swine worldwide; in humans, the vast majority of MAH infections is due to strains belonging to specific genotypes, such as the internal transcribed spacer (ITS)-sequevars Mav-A and Mav-B that mostly cause pulmonary infections in elderly patients and severe disseminated infections in acquired immunodeficiency syndrome patients, respectively. To test whether the different types of infections in distinct patients' populations might reflect a different virulence of the infecting genotypes, MAH human isolates, genotyped by ITS sequencing and MIRU-VNTR minisatellite analysis, were studied for the capacity to infect and replicate in human macrophages in vitro...
January 2018: International Journal of Mycobacteriology
Paulo Ranaivomanana, Mihaja Raberahona, Sedera Rabarioelina, Ysé Borella, Alice Machado, Mamy J De Dieu Randria, Rivo A Rakotoarivelo, Voahangy Rasolofo, Niaina Rakotosamimanana
Background: The primary site of infection for Mycobacterium tuberculosis ( Mtb ) is the alveolar macrophages. However, Mtb can disseminate into other organs and causes extrapulmonary tuberculosis (EPTB). The diagnosis of EPTB is challenging due to relatively inaccessible infectious sites that may be paucibacillary and with clinical symptoms varying by site that are similar to those seen in other diseases. Hence, we sought to identify the expression patterns of a variety of cytokines that may be specific to EPTB from in vitro infections and in the plasma of TB patients...
2018: Frontiers in Microbiology
Nallely Lopez-Lopez, Ana Gabriela Ramos Martinez, Mariana Haydee Garcia-Hernandez, Rogelio Hernandez-Pando, Julio Enrique Castañeda-Delgado, Geanncarlo Lugo-Villarino, Céline Cougoule, Olivier Neyrolles, Bruno Rivas-Santiago, Monica Alejandra Valtierra-Alvarado, Marisela Rubio-Caceres, Jose Antonio Enciso-Moreno, Carmen Judith Serrano
BACKGROUND: Type 2 diabetes (T2D) is a risk factor for the development of tuberculosis (TB), although the associated mechanisms are not known. OBJECTIVES: To study the association between T2D and the basal phenotype of macrophages, and their immune response to Mycobacterium tuberculosis (Mtb) infection. METHODS: We evaluated the influence of T2D on the response of monocyte-derived macrophages (MDM) to Mtb in patients with T2D (n = 10) compared to healthy subjects (n = 9), before and after infection with Mtb clinical isolates bearing different degrees of virulence...
February 19, 2018: Memórias do Instituto Oswaldo Cruz
Martin Rao, Davide Valentini, Alimuddin Zumla, Markus Maeurer
BACKGROUND: New tuberculosis (TB) drug treatment regimens are urgently needed. We evaluated the potential of the histone deacetylase inhibitors (HDIs) valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) to enhance the effects of first-line TB drugs against intracellular Mycobacterium tuberculosis (M. tb). METHODS: M. tb H37Rv cultures were exposed to VPA or SAHA over six days, in the presence or absence of isoniazid (INH) and rifampicin (RIF). The efficacy of VPA and SAHA against intracellular M...
March 1, 2018: International Journal of Infectious Diseases: IJID
Dehua Liu, Ben Chung-Lap Chan, Ling Cheng, Miranda Sin-Man Tsang, Jing Zhu, Chun-Wai Wong, Delong Jiao, Helen Yau-Tsz Chan, Ping Chung Leung, Christopher Wai-Kei Lam, Chun Kwok Wong
The immune system responds to Mycobacterium tuberculosis (MTB) infection by forming granulomas to quarantine the bacteria from spreading. Granuloma-mediated inflammation is a cause of lung destruction and disease transmission. Sophora flavescens (SF) has been demonstrated to exhibit bactericidal activities against MTB. However, its immune modulatory activities on MTB-mediated granulomatous inflammation have not been reported. In the present study, we found that flavonoids from Sophora flavescens (FSF) significantly suppressed the pro-inflammatory mediators released from mouse lung alveolar macrophages (MH-S) upon stimulation by trehalose dimycolate (TDM), the most abundant lipoglycan on MTB surface...
March 2, 2018: Scientific Reports
Lu Huang, Evgeniya V Nazarova, Shumin Tan, Yancheng Liu, David G Russell
To understand how infection by Mycobacterium tuberculosis (Mtb) is modulated by host cell phenotype, we characterized those host phagocytes that controlled or supported bacterial growth during early infection, focusing on the ontologically distinct alveolar macrophage (AM) and interstitial macrophage (IM) lineages. Using fluorescent Mtb reporter strains, we found that bacilli in AM exhibited lower stress and higher bacterial replication than those in IM. Interestingly, depletion of AM reduced bacterial burden, whereas depletion of IM increased bacterial burden...
March 2, 2018: Journal of Experimental Medicine
Christian David Sánchez-Barinas, Marisol Ocampo, Magnolia Vanegas, Jeimmy Johana Castañeda-Ramirez, Manuel Alfonso Patarroyo, Manuel Elkin Patarroyo
Mycobacterium tuberculosis is the causative agent of tuberculosis, a disease causing major mortality worldwide. As part of a systematic methodology for studying M. tuberculosis surface proteins which might be involved in host-pathogen interactions, our group found that LpqG surface protein (Rv3623) found in M. tuberculosis complex strains was located on the mycobacterial envelope and that peptide 16661 (21 SGCDSHNSGSLGADPRQVTVY40 ) had high specific binding to U937 monocyte-derived macrophages and inhibited mycobacterial entry to such cells in a concentration-dependent way...
February 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Hicret Islamoglu, Ruoqiong Cao, Garrett Teskey, Karo Gyurjian, Sebastian Lucar, Marcel P Fraix, Airani Sathananthan, John K Chan, Vishwanath Venketaraman
Mycobacterium tuberculosis ( M. tb ), a rod-shaped acid-fast bacterium, is the causative agent of tuberculosis (TB). TB remains one of the leading causes of morbidity and mortality worldwide. Additionally, approximately one-third of the world's population has latent tuberculosis infection (LTBI) as a result of the body's primary mechanism of defense against M. tb infection, the formation of a granuloma. A granuloma is the aggregation of immune cells that encapsulate the bacteria to keep them localized to prevent further infection and thus the bacteria become quiescent...
March 1, 2018: Journal of Clinical Medicine
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