Escape of Mycobacterium tuberculosis from oxidative killing by neutrophils: Tubercle bacilli escape neutrophil killing
Open accessAbstract
Neutrophils enter sites of infection, where they can eliminate pathogenic bacteria in an oxidative manner. Despite their predominance in active tuberculosis lesions, the function of neutrophils in this important human infection is still highly controversial. We observed that virulent Mycobacterium tuberculosis survived inside human neutrophils despite prompt activation of these defence cells' microbicidal effectors. Survival of M. tuberculosis was accompanied by necrotic cell death of infected neutrophils. Necrotic cell death entirely depended on radical oxygen species production since chronic granulomatous disease neutrophils were protected from M. tuberculosis-triggered necrosis. More, importantly, the M. tuberculosis ΔRD1 mutant failed to induce neutrophil necrosis rendering this strain susceptible to radical oxygen species-mediated killing. We conclude that this virulence function is instrumental for M. tuberculosis to escape killing by neutrophils and contributes to pathogenesis in tuberculosis.
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PMNs from chronic granulomatous disease patients lacking a functional NADPH-oxidase fail to succumb to necrotic cell death by wildtype M. tuberculosis but are also unable to kill attenuated strains.
“Interestingly, PMNs from chronic granulomatous disease patients lacking a functional NADPH-oxidase fail to succumb to necrotic cell death by wildtype M. tuberculosis but are also unable to kill attenuated strains (120).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [120]
Virulent M. tuberculosis strains use ROI-mediated necrosis as an escape mechanism from killing by PMNs.
“These data suggest that virulent M. tuberculosis strains use ROI-mediated necrosis as an escape mechanism from killing by PMNs.”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [120]
Upon co-culture with M. tuberculosis, PMNs actively migrate toward the mycobacteria in vitro and become activated upon phagocytosis, as indicated by ROI production, IL-8 release, and generation of active cathelicidin, MPO, and NETs.
“Upon co-culture with M. tuberculosis, PMNs actively migrate toward the mycobacteria in an in vitro assay and become activated upon phagocytosis as indicated by ROI production, IL-8 release and generation of active cathelicidin, MPO and NETs (120).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [120]
Attenuated M. tuberculosis strains lacking the RD1 genomic virulence region extend the survival of PMNs before apoptotic suicide and are eventually killed in a ROI (MPO, NOX2)-dependent manner.
“In contrast, attenuated M. tuberculosis strains lacking the RD1 genomic virulence region not only extend the survival of PMNs before apoptotic suicide but also eventually kills those attenuated strains in a ROI (MPO, NOX2)-dependent manner.”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [120]
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Self-citation
- Authors
- Corleis, B., Korbel, D., Wilson, R., Bylund, J., Chee, R., & Schaible, U. E.
- Affiliations
- London School of Hygiene & Tropical Medicine (GB)
- University College London (GB)
- University of Gothenburg (SE)
- The Royal Free Hospital (GB)
- Corresponding author
- Schaible, Ulrich E.
- Venue
- Cellular Microbiology
- Publisher
- Hindawi Limited
- Published
- 2012-04-13
- Volume
- 14
- Issue
- 7
- Pages
- 1109-1121
- ISSN
- 1462-5814 (ISSN-L)
- OpenAlex
- W2121632392
- Cited by
- 150
- References
- 52
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 6 · 2023: 13 · 2022: 14 · 2021: 13 · 2020: 8 · 2019: 10 · 2018: 11 · 2017: 14 · 2016: 8 · 2015: 16 · 2014: 7 · 2013: 8 · 2012: 5
- FWCI
- 7.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cellular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
- Funders
- Queen Mary University of London
- London School of Hygiene and Tropical Medicine
- Strong
- Imperial College London
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- Mycobacterium tuberculosis, neutrophils, oxidative killing, bacterial survival in host cells, necrosis, reactive oxygen species, chronic granulomatous disease, bacterial virulence factors, tuberculosis pathogenesis, phagocytosis
- MeSH terms
- Adolescent, Adult, Humans, Mycobacterium tuberculosis, Neutrophils, Virulence, Cell Death, Reactive Oxygen Species, Microbial Viability, Young Adult
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