scholarly journals The Nature of Extracellular Iron Influences Iron Acquisition by Mycobacterium tuberculosis Residing within Human Macrophages

2004 ◽  
Vol 72 (4) ◽  
pp. 2022-2028 ◽  
Author(s):  
Oyebode Olakanmi ◽  
Larry S. Schlesinger ◽  
Ambar Ahmed ◽  
Bradley E. Britigan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Human Lung ◽  
Iron Acquisition ◽  
Human Monocyte ◽  
Low Molecular Weight ◽  
Fe Uptake ◽  
Ifn Γ ◽  
Efficient Mechanisms ◽  
Fe Acquisition ◽  
Exogenous Source

ABSTRACT We have reported that Mycobacterium tuberculosis residing within the phagosomes of human monocyte-derived macrophages (MDM) can acquire Fe from extracellular transferrin (TF) and sources within the MDM. In the lung, Fe is also bound to lactoferrin (LF) and low-molecular-weight chelates. We therefore investigated the ability of intraphagosomal M. tuberculosis to acquire Fe from these sources. M. tuberculosis acquired 30-fold and 3-fold more Fe from LF and citrate, respectively, compared to TF, in spite of similar MDM-associated Fe. M. tuberculosis infection decreased MDM-associated Fe relative to uninfected MDM as follows: TF (38.7%), citrate (21.1%), and LF (15.3%). M. tuberculosis Fe acquisition from extracellular chelates (exogenous source) and from endogenous MDM Fe initially acquired from the three chelates (endogenous source) was compared. M. tuberculosis Fe acquisition was similar from exogenous and endogenous sources supplied as Fe-TF. In contrast, there was much greater intracellular M. tuberculosis Fe uptake from LF and citrate from the exogenous than endogenous source. Gamma interferon (IFN-γ) reduced MDM Fe uptake from each chelate by ∼50% and augmented the M. tuberculosis-induced decrease in MDM Fe uptake from exogenous TF, but not from LF or citrate. IFN-γ minimally decreased intracellular M. tuberculosis Fe acquisition from exogenous Fe-TF but significantly increased Fe uptake from LF and citrate. Intraphagosomal M. tuberculosis Fe acquisition from both exogenous and endogenous MDM sources, and the effect of IFN-γ on this process, is influenced by the nature of the extracellular Fe chelate. M. tuberculosis has developed efficient mechanisms of acquiring Fe from a variety of Fe chelates that it likely encounters within the human lung.

scholarly journals Urban airborne particle exposure impairs human lung and blood Mycobacterium tuberculosis immunity

Thorax ◽  
2019 ◽  
Vol 74 (7) ◽  
pp. 675-683 ◽  
Author(s):  
Martha Torres ◽  
Claudia Carranza ◽  
Srijata Sarkar ◽  
Yolanda Gonzalez ◽  
Alvaro Osornio Vargas ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mexico City ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Human Lung ◽  
Constitutive Expression ◽  
In Vitro Exposure ◽  
Ifn Γ

RationaleAssociations between urban (outdoor) airborne particulate matter (PM) exposure and TB and potential biological mechanisms are poorly explored.ObjectivesTo examine whether in vivo exposure to urban outdoor PM in Mexico City and in vitro exposure to urban outdoor PM2.5 (< 2.5 µm median aerodynamic diameter) alters human host immune cell responses to Mycobacterium tuberculosis.MethodsCellular toxicity (flow cytometry, proliferation assay (MTS assay)), M. tuberculosis and PM2.5 phagocytosis (microscopy), cytokine-producing cells (Enzyme-linked immune absorbent spot (ELISPOT)), and signalling pathway markers (western blot) were examined in bronchoalveolar cells (BAC) and peripheral blood mononuclear cells (PBMC) from healthy, non-smoking, residents of Mexico City (n=35; 13 female, 22 male). In vivo-acquired PM burden in alveolar macrophages (AM) was measured by digital image analysis.Measurements and main resultsIn vitro exposure of AM to PM2.5 did not affect M. tuberculosis phagocytosis. High in vivo-acquired AM PM burden reduced constitutive, M. tuberculosis and PM-induced interleukin-1β production in freshly isolated BAC but not in autologous PBMC while it reduced constitutive production of tumour necrosis factor-alpha in both BAC and PBMC. Further, PM burden was positively correlated with constitutive, PM, M. tuberculosis and purified protein derivative (PPD)-induced interferon gamma (IFN-γ) in BAC, and negatively correlated with PPD-induced IFN-γ in PBMC.ConclusionsInhalation exposure to urban air pollution PM impairs important components of the protective human lung and systemic immune response against M. tuberculosis. PM load in AM is correlated with altered M. tuberculosis-induced cytokine production in the lung and systemic compartments. Chronic PM exposure with high constitutive expression of proinflammatory cytokines results in relative cellular unresponsiveness.

scholarly journals Insights into the chemistry of the amphibactin–metal (M3+) interaction and its role in antibiotic resistance

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vidya Kaipanchery ◽  
Anamika Sharma ◽  
Fernando Albericio ◽  
Beatriz G. de la Torre
Keyword(s):  
Metal Ions ◽  
Iron Uptake ◽  
Pathogenic Bacteria ◽  
Iron Acquisition ◽  
Transition Metal Ions ◽  
Low Molecular Weight ◽  
Acquisition Strategies ◽  
Iron Deficient ◽  
Fe Uptake ◽  
Vibrio Genus

AbstractWe have studied the diversity and specificity of interactions of amphibactin produced by Vibrio genus bacterium (Vibrio sp. HC0601C5) with iron and various metal ions in + 3 oxidation state in an octahedral (Oh) environment. To survive in the iron-deficient environment of their host, pathogenic bacteria have devised various efficient iron acquisition strategies. One such strategy involves the production of low molecular weight peptides called siderophores, which have a strong affinity and specificity to chelate Fe3+ and can thus facilitate uptake of this metal in order to ensure iron requirements. The Fe uptake by amphibactin and the release of iron inside the cell have been studied. Comparison of the interaction of different transition metal ions (M3+) with amphibactin has been studied and it reveals that Co and Ga form stable complexes with this siderophore. The competition of Co and Ga with Fe impedes iron uptake by bacteria, thereby preventing infection.

scholarly journals Cell Envelope Protein PPE68 Contributes to Mycobacterium tuberculosis RD1 Immunogenicity Independently of a 10-Kilodalton Culture Filtrate Protein and ESAT-6

2004 ◽  
Vol 72 (4) ◽  
pp. 2170-2176 ◽  
Author(s):  
Caroline Demangel ◽  
Priscille Brodin ◽  
Paul J. Cockle ◽  
Roland Brosch ◽  
Laleh Majlessi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Culture Filtrate ◽  
Envelope Protein ◽  
Protective Efficacy ◽  
Cell Envelope ◽  
Genomic Region ◽  
Low Molecular Weight ◽  
Ifn Γ ◽  
Culture Filtrate Protein ◽  
Low Molecular Weight Proteins

ABSTRACT The protective efficacy of Mycobacterium bovis BCG can be markedly augmented by stable integration of Mycobacterium tuberculosis genomic region RD1. BCG complemented with RD1 (BCG::RD1) encodes nine additional proteins. Among them, 10-kDa culture filtrate protein (CFP-10) and ESAT-6 (6-kDa early secreted antigenic target) are low-molecular-weight proteins that induce potent Th1 responses. Using pools of synthetic peptides, we have examined the potential immunogenicity of four other RD1 products (PE35, PPE68, Rv3878, and Rv3879c). PPE68, the protein encoded by rv3873, was the only one to elicit gamma interferon (IFN-γ)-producing cells in C57BL/6 mice infected with M. tuberculosis. Anti-PPE68 T cells were predominantly raised against an epitope mapped in the N-terminal end of the protein. Importantly, inactivation of rv3873 in BCG::RD1 did not modify CFP-10 and ESAT-6 secretion. Moreover, the generation of IFN-γ responses to these antigens following immunization with BCG::RD1 was independent of PPE68 expression. Taken together, these results show that PPE68 is an immunogenic product of the RD1 region, which does not interfere with the secretion and immunogenicity of CFP-10 and ESAT-6.

scholarly journals IntraphagosomalMycobacterium tuberculosisAcquires Iron from Both Extracellular Transferrin and Intracellular Iron Pools

2002 ◽  
Vol 277 (51) ◽  
pp. 49727-49734 ◽  
Author(s):  
Oyebode Olakanmi ◽  
Larry S. Schlesinger ◽  
Ambar Ahmed ◽  
Bradley E. Britigan
Keyword(s):  
Iron Acquisition ◽  
Hereditary Hemochromatosis ◽  
Human Monocyte ◽  
Interferon Γ ◽  
Receptor Expression ◽  
Intracellular Growth ◽  
Intracellular Iron ◽  
Healthy Donors ◽  
Viable Bacteria ◽  
Ifn Γ

Mycobacterium tuberculosismultiplies within the macrophage phagosome and requires iron for growth. We examined the route(s) by which intracellularM. tuberculosisacquires iron. During intracellular growth of the virulent ErdmanM. tuberculosisstrain in human monocyte-derived macrophages (MDM),M. tuberculosisacquisition of59Fe from transferrin (TF) provided extracellularly (exogenous source) was compared with acquisition when MDM were loaded with59Fe from TF prior toM. tuberculosisinfection (endogenous sources).M. tuberculosis59Fe acquisition required viable bacteria and was similar from exogenous and endogenous sources at 24 h and greater from exogenous iron at 48 h. Interferon-γ treatment of MDM reduced59Fe uptake from TF 51% and TF receptor expression by 34%. Despite this, intraphagosomalM. tuberculosisiron acquisition in IFN-γ-treated cells was decreased by only 30%. Macrophages from hereditary hemochromatosis patients have altered iron metabolism. IntracellularM. tuberculosisacquired markedly less iron in MDM from these individuals than in MDM from healthy donors, regardless of the iron source (exogenous and endogenous): 36 ± 3.8% and 17 ± 9.6% of control, respectively. Thus, intraphagosomalM. tuberculosiscan acquire iron from both extracellular TF and endogenous macrophage sources. Acquisition of iron from macrophage cytoplasmic iron pools may be critical for the intracellular growth ofM. tuberculosis. This acquisition is altered by IFN-γ treatment to a small extent, but is markedly reduced in macrophages from hemochromatosis patients.

scholarly journals Cytokine Biosignature of Active and Latent Mycobacterium Tuberculosis Infection in Children

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 517
Author(s):  
Magdalena Druszczynska ◽  
Michal Seweryn ◽  
Sebastian Wawrocki ◽  
Magdalena Kowalewska-Pietrzak ◽  
Anna Pankowska ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Mediators ◽  
Latent Tuberculosis ◽  
Serum Levels ◽  
Diagnostic Tools ◽  
Mycobacterium Tuberculosis Infection ◽  
Only Children ◽  
Latent Tb ◽  
Ifn Γ ◽  
Multiplex Bead

None of the currently used diagnostic tools are efficient enough in diagnosing Mycobacterium tuberculosis (M.tb) infection in children. The study was aimed to identify cytokine biosignatures characterizing active and latent tuberculosis (TB) in children. Using a multiplex bead-based technology, we analyzed the levels of 53 Th17-related cytokines and inflammatory mediators in sera from 216 BCG-vaccinated children diagnosed with active TB (TB) or latent TB (LTBI) as well as uninfected controls (HC). Children with active TB, compared to HC children, showed reduced serum levels of IL-17A, MMP-2, OPN, PTX-3, and markedly elevated concentrations of APRIL/TNFSF13. IL-21, sCD40L, MMP-2, and IL-8 were significantly differentially expressed in the comparisons between groups: (1) HC versus TB and LTBI (jointly), and (2) TB versus LTBI. The panel consisting of APRIL/TNFSF13, sCD30/TNFRSF8, IFN-α2, IFN-γ, IL-2, sIL-6Rα, IL-8, IL-11, IL-29/IFN-λ1, LIGHT/TNFSF14, MMP-1, MMP-2, MMP-3, osteocalcin, osteopontin, TSLP, and TWEAK/TNFSF12 possessed a discriminatory potential for the differentiation between TB and LTBI children. Serum-based host biosignatures carry the potential to aid the diagnosis of childhood M.tb infections. The proposed panels of markers allow distinguishing not only children infected with M.tb from uninfected individuals but also children with active TB from those with latent TB.

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