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Mycobacterium macrophages

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https://www.readbyqxmd.com/read/29791904/the-cgas-sting-pathway-is-important-for-dendritic-cell-activation-but-is-not-essential-to-induce-protective-immunity-against-mycobacterium-tuberculosis-infection
#1
Fabio V Marinho, Sulayman Benmerzoug, Stephanie Rose, Priscila C Campos, João T Marques, André Báfica, Glen Barber, Bernhard Ryffel, Sergio C Oliveira, Valerie F J Quesniaux
Mycobacterium tuberculosis (Mtb) infection remains a major public health concern. The STING (stimulator of interferon genes) pathway contributes to the cytosolic surveillance of host cells. Most studies on the role of STING activation in Mtb infection have focused on macrophages. Moreover, a detailed investigation of the role of STING during Mtb infection in vivo is required. Here, we deciphered the involvement of STING in the activation of dendritic cells (DCs) and the host response to Mtb infection in vivo...
May 23, 2018: Journal of Innate Immunity
https://www.readbyqxmd.com/read/29789389/lrrk2-is-a-negative-regulator-of-mycobacterium-tuberculosis-phagosome-maturation-in-macrophages
#2
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...
May 22, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29782535/mycobacterium-tuberculosis-specific-cd4-and-cd8-t-cells-differ-in-their-capacity-to-recognize-infected-macrophages
#3
Jason D Yang, Daniel Mott, Rujapak Sutiwisesak, Yu-Jung Lu, Fiona Raso, Britni Stowell, Greg Hunter Babunovic, Jinhee Lee, Steve M Carpenter, Sing Sing Way, Sarah M Fortune, Samuel M Behar
Containment of Mycobacterium tuberculosis (Mtb) infection requires T cell recognition of infected macrophages. Mtb has evolved to tolerate, evade, and subvert host immunity. Despite a vigorous and sustained CD8+ T cell response during Mtb infection, CD8+ T cells make limited contribution to protection. Here, we ask whether the ability of Mtb-specific T cells to restrict Mtb growth is related to their capacity to recognize Mtb-infected macrophages. We derived CD8+ T cell lines that recognized the Mtb immunodominant epitope TB10...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29781535/mir-1178-regulates-mycobacterial-survival-and-inflammatory-responses-in-mycobacterium-tuberculosis-infected-macrophages-partly-via-tlr4
#4
Ge Shi, Guofeng Mao, Kejie Xie, Dongdong Wu, Wei Wang
Tuberculosis is chronic respiratory infectious disease and is caused by the infection of Mycobacterium tuberculosis (M.tb). Macrophages play an important role in host immune response against M.tb infection, which is regulated by various factors, including microRNAs (miRNAs). The present study aimed to examine the in vitro functional role of miR-1178 in mycobacterial survival and inflammatory responses induced by M.tb infection in human macrophages. Our results showed that M.tb infection increased the expression of miR-1178 in human macrophages (HTP-1 and U937 cells) in a concentration- and time-dependent manner...
May 21, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29779777/interleukin-23-interleukin-17-axis-activated-by-mycobacterium-avium-complex-mac-is-attenuated-in-patients-with-mac-lung-disease
#5
Chin-Chung Shu, Jann-Yuan Wang, Ming-Fang Wu, Hsin-Chih Lai, Bor-Luen Chiang, Chong-Jen Yu
BACKGROUND: Mycobacterium avium complex (MAC)-lung disease (LD) is increasing in patients without human immunodeficiency virus infection. However, data on host vulnerability to MAC-related immune responses, and in particular the interleukin (IL)-23/IL-17 axis, are lacking. METHODS: We enrolled 50 patients with MAC-LD, 25 age-matched patients with tuberculosis (TB) and 25 controls. We measured levels of plasma cytokines, and studied IL-12/IL-17 responses in macrophage and lymphocyte activation to MAC...
May 2018: Tuberculosis
https://www.readbyqxmd.com/read/29773170/iron-and-innate-antimicrobial-immunity-depriving-the-pathogen-defending-the-host
#6
REVIEW
Manfred Nairz, Stefanie Dichtl, Andrea Schroll, David Haschka, Piotr Tymoszuk, Igor Theurl, Günter Weiss
The acute-phase response is triggered by the presence of infectious agents and danger signals which indicate hazards for the integrity of the mammalian body. One central feature of this response is the sequestration of iron into storage compartments including macrophages. This limits the availability of this essential nutrient for circulating pathogens, a host defence strategy known as 'nutritional immunity'. Iron metabolism and the immune response are intimately linked. In infections, the availability of iron affects both the efficacy of antimicrobial immune pathways and pathogen proliferation...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29771143/cell-envelope-lipids-in-the-pathophysiology-of-mycobacterium-tuberculosis
#7
Parul Singh, Nagender Rao Rameshwaram, Sudip Ghosh, Sangita Mukhopadhyay
Mycobacterium tuberculosis is an intracellular bacterium that persists and replicates inside macrophages. The bacterium possesses an unusual lipid-rich cell envelope that provides a hydrophobic impermeable barrier against many environmental stressors and allows it to survive extremely hostile intracellular surroundings. Since the lipid-rich envelope is crucial for M. tuberculosis virulence, the components of the cell wall lipid biogenesis pathways constitute an attractive target for the development of vaccines and antimycobacterial chemotherapeutics...
May 17, 2018: Future Microbiology
https://www.readbyqxmd.com/read/29767993/multi-metallic-microparticles-increase-the-potency-of-rifampicin-against-intracellular-mycobacterium-tuberculosis
#8
Timothy Ellis, Michele Chiappi, Andres Garcia-Trenco, Maryam Al-Ejji, Srijata Sarkar, Theoni K Georgiou, Milo Sebastian Peter Shaffer, Teresa D Tetley, Stephan Schwander, Mary P Ryan, Alexandra E Porter
Mycobacterium tuberculosis (M.tb) has the extraordinary ability to adapt to the administration of antibiotics through the development of resistance mechanisms. By rapidly exporting drugs from within the cytosol, these pathogenic bacteria diminish antibiotic potency and drive the presentation of drug tolerant tuberculosis (TB). The membrane integrity of M.tb is pivotal in retaining these drug-resistant traits. Silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) are established antimicrobial agents that effectively compromise membrane stability, giving rise to increased bacterial permeability to antibiotics...
May 16, 2018: ACS Nano
https://www.readbyqxmd.com/read/29765372/is-iqg-607-a-potential-metallodrug-or-metallopro-drug-with-a-defined-molecular-target-in-mycobacterium-tuberculosis
#9
REVIEW
Bruno L Abbadi, Valnês da Silva Rodrigues-Junior, Adilio da Silva Dadda, Kenia Pissinate, Anne D Villela, Maria M Campos, Luiz G de França Lopes, Cristiano V Bizarro, Pablo Machado, Eduardo H S Sousa, Luiz A Basso
The emergence of strains of Mycobacterium tuberculosis resistant to isoniazid (INH) has underscored the need for the development of new anti-tuberculosis agents. INH is activated by the mycobacterial katG -encoded catalase-peroxidase, forming an acylpyridine fragment that is covalently attached to the C4 of NADH. This isonicotinyl-NAD adduct inhibits the activity of 2- trans -enoyl-ACP(CoA) reductase (InhA), which plays a role in mycolic acid biosynthesis. A metal-based INH analog, Na3 [FeII (CN)5 (INH)]·4H2 O, IQG-607, was designed to have an electronic redistribution on INH moiety that would lead to an intramolecular electron transfer to bypass KatG activation...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29764842/role-of-the-hepcidin-ferroportin-axis-in-pathogen-mediated-intracellular-iron-sequestration-in-human-phagocytic-cells
#10
Rodrigo Abreu, Frederick Quinn, Pramod K Giri
Upon infection, pathogen and host compete for the same iron pool, because this trace metal is a crucial micronutrient for all living cells. Iron dysregulation in the host is strongly associated with poor outcomes in several infectious diseases, including tuberculosis, AIDS, and malaria, and inefficient iron scavenging by pathogens severely affects their virulence. Hepcidin is the master regulator of iron homeostasis in vertebrates, responsible for diminishing iron export from macrophages during iron overload or infection...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29762680/tuberculosis-and-the-art-of-macrophage-manipulation
#11
S Upadhyay, E Mittal, J A Philips
Macrophages are first-line responders against microbes. The success of Mycobacterium tuberculosis (Mtb) rests upon its ability to convert these antimicrobial cells into a permissive cellular niche. This is a remarkable accomplishment, as the antimicrobial arsenal of macrophages is extensive. Normally bacteria are delivered to an acidic, degradative lysosome through one of several trafficking pathways, including LC3-associated phagocytosis (LAP) and autophagy. Once phagocytozed, the bacilli are subjected to reactive oxygen and nitrogen species, and they induce the expression of proinflammatory cytokines, which serve to augment host responses...
June 1, 2018: Pathogens and Disease
https://www.readbyqxmd.com/read/29760437/cd82-hypomethylation-is-essential-for-tuberculosis-pathogenesis-via-regulation-of-runx1-rab5-22
#12
Hyun-Jung Koh, Ye-Ram Kim, Jae-Sung Kim, Jin-Seung Yun, Sojin Kim, Sun Young Kim, Kiseok Jang, Chul-Su Yang
The tumor suppressor gene CD82/KAI1 is a member of the tetraspanin superfamily and organizes various membrane-based processes. Mycobacterium tuberculosis (MTB) persists in host macrophages by interfering with phagolysosome biogenesis and inflammatory responses, but the role of CD82 in controlling the intracellular survival of pathogenic mycobacteria within macrophages remains poorly understood. In this study, we demonstrated that the virulent MTB strain H37Rv (MTB Rv) induced CD82 promoter hypomethylation, resulting in CD82 expression...
May 14, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29758082/adjunct-antibody-administration-with-standard-treatment-reduces-relapse-rates-in-a-murine-tuberculosis-model-of-necrotic-granulomas
#13
Alvaro A Ordonez, Supriya Pokkali, Sunhwa Kim, Brian Carr, Mariah H Klunk, Leah Tong, Vikram Saini, Yong S Chang, Matthew McKevitt, Victoria Smith, David L Gossage, Sanjay K Jain
Matrix metalloproteinase (MMP)-9 is a zinc-dependent protease associated with early immune responses to Mycobacterium tuberculosis infection, macrophage recruitment and granuloma formation. We evaluated whether adjunctive inhibition of MMP-9 could improve the response to standard TB treatment in a mouse model that develops necrotic lesions. Six weeks after an aerosol infection with M. tuberculosis, C3HeB/FeJ mice received standard TB treatment (12 weeks) comprising rifampin, isoniazid and pyrazinamide alone or in combination with either anti-MMP-9 antibody, etanercept (positive control) or isotype antibody (negative control) for 6 weeks...
2018: PloS One
https://www.readbyqxmd.com/read/29755479/lysophosphatidylcholine-promotes-phagosome-maturation-and-regulates-inflammatory-mediator-production-through-the-protein-kinase-a-phosphatidylinositol-3-kinase-p38-mitogen-activated-protein-kinase-signaling-pathway-during-mycobacterium-tuberculosis-infection
#14
Hyo-Ji Lee, Hyun-Jeong Ko, Dong-Kun Song, Yu-Jin Jung
Tuberculosis is caused by the infectious agent Mycobacterium tuberculosis (Mtb). Mtb has various survival strategies, including blockade of phagosome maturation and inhibition of antigen presentation. Lysophosphatidylcholine (LPC) is a major phospholipid component of oxidized low-density lipoprotein and is involved in various cellular responses, such as activation of second messengers and bactericidal activity in neutrophils. In this study, macrophages were infected with a low infectious dose of Mtb and treated with LPC to investigate the bactericidal activity of LPC against Mtb...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29749650/irak4-activity-controls-immune-responses-to-intracellular-bacteria-listeria-monocytogenes-and-mycobacterium-smegmatis
#15
Goutham Pattabiraman, Michael Murphy, Federica Agliano, Keaton Karlinsey, Andrei E Medvedev
IL-1 receptor-associated kinase (IRAK) 4 is a central enzyme of the TLR pathways. This study tested the hypothesis that IRAK4 kinase activity is prerequisite for regulating innate immunity during infections with intracellular bacteria. To this end, we analyzed responses of macrophages obtained from mice expressing wild-type (WT) IRAK4 or its kinase-inactive K213M mutant (IRAK4KI ) upon infection with intracellular bacteria Listeria monocytogenes or Mycobacterium smegmatis. In contrast to robust induction of cytokines by macrophages expressing kinase-sufficient IRAK4, IRAK4KI macrophages expressed decreased TNF-α, IL-6, IL-1β, and C-C motif chemokine ligand 5 upon infection with L...
May 11, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29749044/mycobacteria-employ-two-different-mechanisms-to-cross-the-blood-brain-barrier
#16
L M van Leeuwen, M Boot, C Kuijl, D I Picavet, G van den Brink, S M A van der Pol, H E de Vries, N N van der Wel, M van der Kuip, A M van Furth, A M van der Sar, W Bitter
Central nervous system (CNS) infection by Mycobacterium tuberculosis is one of the most devastating complications of tuberculosis, in particular in early childhood. In order to induce CNS infection, M. tuberculosis needs to cross specialized barriers protecting the brain. How M. tuberculosis crosses the blood-brain barrier (BBB) and enters the CNS is not well understood. Here, we use transparent zebrafish larvae and the closely related pathogen Mycobacterium marinum to answer this question. We show that in the early stages of development mycobacteria rapidly infect brain tissue, either as free mycobacteria or within circulating macrophages...
May 10, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29740038/heparin-inhibits-intracellular-mycobacterium-tuberculosis-bacterial-replication-by-reducing-iron-levels-in-human-macrophages
#17
Rodrigo Abreu, Lauren Essler, Allyson Loy, Frederick Quinn, Pramod Giri
Iron is a crucial micronutrient for both mammals and their associated pathogens, and extensive literature has shown that Mycobacterium tuberculosis (Mtb) bacilli inhibited from acquiring iron from the host are severely attenuated. In contrast, increased dietary iron concentrations or patients with hemochromatosis have long been associated with a more severe tuberculosis (TB) disease outcome. We have observed that upon macrophage infection, Mtb bacilli strongly promote intracellular iron sequestration, both through increased expression of hepcidin, a key mammalian iron regulatory protein, and downregulation of the iron exporter protein, ferroportin...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29739437/induction-of-the-acid-inducible-lipf-promoter-is-reversibly-inhibited-in-ph-ranges-of-ph-4-2-4-0
#18
Rachelle Torres, Donna Dorriz, Beatrice Saviola
OBJECTIVE: In the human body pathogenic mycobacteria encounter low pH within the phagosomes of macrophages where they reside after being internalized by the host cell. Low pH within macrophages has been shown to induce expression of a variety of genes within these bacteria. It had been previously observed that the Mycobacterium tuberculosis lipF promoter is transcriptionally upregulated between pHs 4.5-6.4 in Mycobacterium smegmatis, with an upper pH limit of 6.4 capable of promoter induction...
May 8, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29735762/two-dd-carboxypeptidases-from-mycobacterium-smegmatis-affect-cell-surface-properties-through-regulation-of-peptidoglycan-cross-linking-and-glycopeptidolipids
#19
Satya Deo Pandey, Shilpa Pal, Ganesh Kumar N, Ankita Bansal, Sathi Mallick, Anindya S Ghosh
During the peptidoglycan (PG) maturation of mycobacteria, the glycan strands are interlinked by both 3-3 (between two meso-DAP) and 4-3 cross-links (between D-ala and meso-DAP), though there is a predominance (60-80%) of 3-3 cross-links. The DD-CPases act on pentapeptides to generate tetrapeptides that are used by LD-transpeptidases as substrates to form 3-3 cross-links. Therefore, DD-CPases play a crucial role in mycobacterial PG cross-link formation. However, the physiology of DD-CPases in mycobacteria is relatively unexplored...
May 7, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29728127/immunohistochemical-characterization-of-tuberculous-lesions-in-sheep-naturally-infected-with-mycobacterium-bovis
#20
Raquel Vallejo, Juan Francisco García Marín, Ramón Antonio Juste, Marta Muñoz-Mendoza, Francisco Javier Salguero, Ana Balseiro
BACKGROUND: Sheep have been traditionally considered as less susceptible to Mycobacterium bovis (Mbovis) infection than other domestic ruminants such as cattle and goats. However, there is increasing evidence for the role of this species as a domestic Mbovis reservoir, mostly when sheep share grazing fields with infected cattle and goats. Nevertheless, there is a lack of information about the pathogenesis and the immune response of Mbovis infection in sheep. The goals of this study were to characterize the granuloma stages produced by the natural infection of Mbovis in sheep, to compare them with other species and to identify possible differences in the sheep immune response...
May 4, 2018: BMC Veterinary Research
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