Delay of phagosome maturation by a mycobacterial lipid is reversed by nitric oxide
Open accessAbstract
Mycobacterium tuberculosis is a facultative intracellular pathogen that inhibits phagosome maturation in macrophages thereby securing survival and growth. Mycobacteria reside in an early endocytic compartment of near-neutral pH where they upregulate production of complex glycolipids such as trehalose dimycolate. Here, we report that trehalose dimycolate coated onto beads increased the bead retention in early phagosomes, i.e. at a similar stage as viable mycobacteria. Thus, a single mycobacterial lipid sufficed to divert phagosome maturation and likely contributes to mycobacterial survival in macrophages. Previous studies showed that activated macrophages promote maturation of mycobacterial phagosomes and eliminate mycobacteria through bactericidal effectors including nitric oxide generated by inducible nitric-oxide synthase. We show that deceleration of bead phagosome maturation by trehalose dimycolate was abolished in immune-activated wild type, but not in activated nitric-oxide synthase-deficient macrophages, nor when hydroxyl groups of trehalose dimycolate were chemically modified by reactive nitrogen intermediates. Thus, specific host defence effectors of activated macrophages directly target a specific virulence function of mycobacteria.
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The mycobacterial cord factor TDM delays phagosome maturation when coated onto beads.
“Similarly, the mycobacterial cord factor TDM has been shown to delay phagosome maturation when coated onto beads (9).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [9]
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Self-citation
- Authors
- Axelrod, S., Oschkinat, H., Enders, J., Schlegel, B., Brinkmann, V., Kaufmann, S. H. E., Haas, A., & Schaible, U. E.
- Affiliations
- Max Planck Institute for Infection Biology (DE)
- Leibniz-Forschungsinstitut für Molekulare Pharmakologie (DE)
- University of Bonn (DE)
- Corresponding author
- Schaible, Ulrich E.
- ORCID
- Venue
- Cellular Microbiology
- Publisher
- Hindawi Limited
- Published
- 2008-07
- Volume
- 10
- Issue
- 7
- Pages
- 1530-1545
- ISSN
- 1462-5814 (ISSN-L)
- 1462-5822
- OpenAlex
- W2076631817
- Cited by
- 141
- References
- 52
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 7 · 2021: 5 · 2020: 9 · 2019: 8 · 2018: 8 · 2017: 12 · 2016: 8 · 2015: 11 · 2014: 10 · 2013: 8 · 2012: 11
- FWCI
- 8.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cellular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Max Planck Institute for Plasma Physics (submittedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
- Funders
- Wellcome Trust (082825/Z/07/Z)
- Royal Society
- Centre National de la Recherche Scientifique
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Keywords
- phagosome maturation, Mycobacterium tuberculosis, trehalose dimycolate, nitric oxide, inducible nitric oxide synthase, macrophages, mycobacterial virulence factors, reactive nitrogen intermediates, host-pathogen interaction, intracellular survival
- MeSH terms
- Adjuvants, Immunologic, Animals, Cells, Cultured, Cord Factors, Humans, Hydrogen-Ion Concentration, Interferon-gamma, Lipopolysaccharides, Macrophage Activation, Macrophages, Mice, Inbred C57BL, Molsidomine, Mycobacterium, Nitric Oxide, Phagocytosis, Phagosomes, Immunomagnetic Separation, Nitric Oxide Donors, Reactive Nitrogen Species, Green Fluorescent Proteins, Mice, Nitric Oxide Synthase Type II
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