The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Virulent clinical isolates of Mycobacterium tuberculosis grow rapidly and induce cellular necrosis but minimal apoptosis in murine macrophages
Abstract
In this study, we investigated the ability of four clinical isolates of Mycobacterium tuberculosis representing a range of virulence for their capacity to grow in bone marrow-derived macrophages. The rate of growth of each of the isolates in macrophages reflected their known virulence, but the most virulent isolates strongly induced production of the cytokine tumor necrosis factor α. A key difference, however, was the degree of cell cytotoxicity observed with the more virulent strains ater several days in culture. Staining of cell monolayers for DNA fragmentation indicative of apoptosis showed that this was minimal and only evident to any degree in macrophages infected with the most virulent strains. In contrast, electron microscopy revealed damage of macrophages consistent with cell necrosis. These results suggest that rapid intracellular growth rate and induction of necrotic cell death within host macrophages are virulence factors of M. tuberculosis in the early stages of bacterial infection. They further imply that infected cell apoptosis, regarded as a defense mechanism or cross-priming mechanism, plays a minimal role.
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“Certain virulent M. tuberculosis strains trigger necrosis by inner mitochondrial membrane rupture (124–127).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [127]
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Metadata
- Authors
- Park, J. S., Tamayo, M. H., Gonzalez-Juarrero, M., Orme, I. M., & Ordway, D. J.
- Affiliations
- Colorado State University (US)
- Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University , Fort Collins
- Corresponding author
- Orme, Ian M
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-11-07
- Volume
- 79
- Issue
- 1
- Pages
- 80-86
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2073977907
- Cited by
- 128
- References
- 48
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 10 · 2014: 9 · 2013: 12 · 2012: 10
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AI-40488, AI-44072)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
- Keywords
- Mycobacterium tuberculosis, virulence factors, macrophage infection, intracellular bacterial growth, necrosis, apoptosis, TNF-α, bone marrow-derived macrophages, clinical isolates, DNA fragmentation, host defense
- MeSH terms
- Animals, Bone Marrow Cells, Cell Survival, Cells, Cultured, Female, Humans, Macrophages, Mycobacterium tuberculosis, Necrosis, Tuberculosis, Mice, DNA Fragmentation
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