Induction of cell death in human macrophages by a highly virulent Korean isolate of Mycobacterium tuberculosis and the virulent strain H37Rv

H. Sohn, K. S. Lee, S. Y. Kim, D. M. Shin, SungJae Shin, E. K. Jo, J. K. Park, H. J. Kim

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Recent studies have suggested that virulent strains of Mycobacterium tuberculosis induce apoptosis in macrophages less often than do attenuated strains. K-strain, which belongs to the Beijing family, is the most frequently isolated clinical strain of M. tuberculosis in Korea. In this study, we investigated the differential induction of cell death in human monocytic THP-1 cells by K-strain and H37Rv, a virulent but laboratory-adapted strain of M. tuberculosis. Although no significant difference in growth rate was observed between the cells exposed to K-strain and those exposed to H37Rv, the levels of protective cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-12p40 were lower in K-strain-infected cells than in H37Rv-infected cells. Cell viability assays showed that both K-strain and H37Rv, but not heat- or streptomycin-killed bacteria, induced THP-1 cell death in a TNF-independent manner. In contrast, double staining with fluorochrome-labelled inhibitors of caspase and propidium iodide and lactate dehydrogenase release assays revealed that K-strain induced significantly higher levels of necrotic cell death, rather than apoptosis, in THP-1 cells than did H37Rv. Anti-apoptotic Bcl-2, Mcl-1, Bfl-1 and Bcl-xL in the cells were significantly upregulated following infection with K-strain compared with H37Rv, whereas Bax was slightly upregulated in response to infection with both H37Rv and K-strain. These results suggest that the highly virulent K-strain keeps cellular apoptosis as a host defense mechanism to a minimum and induces necrosis in macrophages.

Original languageEnglish
Pages (from-to)43-50
Number of pages8
JournalScandinavian Journal of Immunology
Volume69
Issue number1
DOIs
Publication statusPublished - 2009 Jan 1

Fingerprint

Mycobacterium tuberculosis
Cell Death
Macrophages
Apoptosis
Tumor Necrosis Factor-alpha
Caspase Inhibitors
Propidium
Interleukins
Streptomycin
Korea
Infection
Fluorescent Dyes
L-Lactate Dehydrogenase
Interleukin-6
Cell Survival
Necrosis
Hot Temperature
Staining and Labeling
Cytokines
Bacteria

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Sohn, H. ; Lee, K. S. ; Kim, S. Y. ; Shin, D. M. ; Shin, SungJae ; Jo, E. K. ; Park, J. K. ; Kim, H. J. / Induction of cell death in human macrophages by a highly virulent Korean isolate of Mycobacterium tuberculosis and the virulent strain H37Rv. In: Scandinavian Journal of Immunology. 2009 ; Vol. 69, No. 1. pp. 43-50.
@article{f78f59c1d9594137ae7c8f8c934f39f0,
title = "Induction of cell death in human macrophages by a highly virulent Korean isolate of Mycobacterium tuberculosis and the virulent strain H37Rv",
abstract = "Recent studies have suggested that virulent strains of Mycobacterium tuberculosis induce apoptosis in macrophages less often than do attenuated strains. K-strain, which belongs to the Beijing family, is the most frequently isolated clinical strain of M. tuberculosis in Korea. In this study, we investigated the differential induction of cell death in human monocytic THP-1 cells by K-strain and H37Rv, a virulent but laboratory-adapted strain of M. tuberculosis. Although no significant difference in growth rate was observed between the cells exposed to K-strain and those exposed to H37Rv, the levels of protective cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-12p40 were lower in K-strain-infected cells than in H37Rv-infected cells. Cell viability assays showed that both K-strain and H37Rv, but not heat- or streptomycin-killed bacteria, induced THP-1 cell death in a TNF-independent manner. In contrast, double staining with fluorochrome-labelled inhibitors of caspase and propidium iodide and lactate dehydrogenase release assays revealed that K-strain induced significantly higher levels of necrotic cell death, rather than apoptosis, in THP-1 cells than did H37Rv. Anti-apoptotic Bcl-2, Mcl-1, Bfl-1 and Bcl-xL in the cells were significantly upregulated following infection with K-strain compared with H37Rv, whereas Bax was slightly upregulated in response to infection with both H37Rv and K-strain. These results suggest that the highly virulent K-strain keeps cellular apoptosis as a host defense mechanism to a minimum and induces necrosis in macrophages.",
author = "H. Sohn and Lee, {K. S.} and Kim, {S. Y.} and Shin, {D. M.} and SungJae Shin and Jo, {E. K.} and Park, {J. K.} and Kim, {H. J.}",
year = "2009",
month = "1",
day = "1",
doi = "10.1111/j.1365-3083.2008.02188.x",
language = "English",
volume = "69",
pages = "43--50",
journal = "Scandinavian Journal of Immunology",
issn = "0300-9475",
publisher = "Wiley-Blackwell",
number = "1",

}

Induction of cell death in human macrophages by a highly virulent Korean isolate of Mycobacterium tuberculosis and the virulent strain H37Rv. / Sohn, H.; Lee, K. S.; Kim, S. Y.; Shin, D. M.; Shin, SungJae; Jo, E. K.; Park, J. K.; Kim, H. J.

In: Scandinavian Journal of Immunology, Vol. 69, No. 1, 01.01.2009, p. 43-50.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Induction of cell death in human macrophages by a highly virulent Korean isolate of Mycobacterium tuberculosis and the virulent strain H37Rv

AU - Sohn, H.

AU - Lee, K. S.

AU - Kim, S. Y.

AU - Shin, D. M.

AU - Shin, SungJae

AU - Jo, E. K.

AU - Park, J. K.

AU - Kim, H. J.

PY - 2009/1/1

Y1 - 2009/1/1

N2 - Recent studies have suggested that virulent strains of Mycobacterium tuberculosis induce apoptosis in macrophages less often than do attenuated strains. K-strain, which belongs to the Beijing family, is the most frequently isolated clinical strain of M. tuberculosis in Korea. In this study, we investigated the differential induction of cell death in human monocytic THP-1 cells by K-strain and H37Rv, a virulent but laboratory-adapted strain of M. tuberculosis. Although no significant difference in growth rate was observed between the cells exposed to K-strain and those exposed to H37Rv, the levels of protective cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-12p40 were lower in K-strain-infected cells than in H37Rv-infected cells. Cell viability assays showed that both K-strain and H37Rv, but not heat- or streptomycin-killed bacteria, induced THP-1 cell death in a TNF-independent manner. In contrast, double staining with fluorochrome-labelled inhibitors of caspase and propidium iodide and lactate dehydrogenase release assays revealed that K-strain induced significantly higher levels of necrotic cell death, rather than apoptosis, in THP-1 cells than did H37Rv. Anti-apoptotic Bcl-2, Mcl-1, Bfl-1 and Bcl-xL in the cells were significantly upregulated following infection with K-strain compared with H37Rv, whereas Bax was slightly upregulated in response to infection with both H37Rv and K-strain. These results suggest that the highly virulent K-strain keeps cellular apoptosis as a host defense mechanism to a minimum and induces necrosis in macrophages.

AB - Recent studies have suggested that virulent strains of Mycobacterium tuberculosis induce apoptosis in macrophages less often than do attenuated strains. K-strain, which belongs to the Beijing family, is the most frequently isolated clinical strain of M. tuberculosis in Korea. In this study, we investigated the differential induction of cell death in human monocytic THP-1 cells by K-strain and H37Rv, a virulent but laboratory-adapted strain of M. tuberculosis. Although no significant difference in growth rate was observed between the cells exposed to K-strain and those exposed to H37Rv, the levels of protective cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-12p40 were lower in K-strain-infected cells than in H37Rv-infected cells. Cell viability assays showed that both K-strain and H37Rv, but not heat- or streptomycin-killed bacteria, induced THP-1 cell death in a TNF-independent manner. In contrast, double staining with fluorochrome-labelled inhibitors of caspase and propidium iodide and lactate dehydrogenase release assays revealed that K-strain induced significantly higher levels of necrotic cell death, rather than apoptosis, in THP-1 cells than did H37Rv. Anti-apoptotic Bcl-2, Mcl-1, Bfl-1 and Bcl-xL in the cells were significantly upregulated following infection with K-strain compared with H37Rv, whereas Bax was slightly upregulated in response to infection with both H37Rv and K-strain. These results suggest that the highly virulent K-strain keeps cellular apoptosis as a host defense mechanism to a minimum and induces necrosis in macrophages.

UR - http://www.scopus.com/inward/record.url?scp=58149083427&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149083427&partnerID=8YFLogxK

U2 - 10.1111/j.1365-3083.2008.02188.x

DO - 10.1111/j.1365-3083.2008.02188.x

M3 - Article

VL - 69

SP - 43

EP - 50

JO - Scandinavian Journal of Immunology

JF - Scandinavian Journal of Immunology

SN - 0300-9475

IS - 1

ER -