Cited by 128Tuberculosis Research and EpidemiologyMycobacterium research and diagnosisInfectious Diseases and Tuberculosis

Virulent clinical isolates of Mycobacterium tuberculosis grow rapidly and induce cellular necrosis but minimal apoptosis in murine macrophages

Park, Jae Seuk, Tamayo, Marcela Henao, Gonzalez-Juarrero, Mercedes, Orme, Ian M, Ordway, Diane J·2005·Journal of Leukocyte Biology

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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Crossref · 10.1189/jlb.0505250

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48 of 48 references verified0 citation errors · 0 not checkable

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  • Certain virulent M. tuberculosis strains trigger necrosis by inner mitochondrial membrane rupture.

    “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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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
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 › Surgery › 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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