Induction of macrophage death by clinical strains of Mycobacterium kansasii

Hosung Sohn, Kwang Wook Kim, Hyun Bae Kang, Choul Jae Won, Woo Sik Kim, Byungsoo Lee, O. Jung Kwon, Won Jung Koh, SungJae Shin, Hwa Jung Kim

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Mycobacterium kansasii is a facultative intracellular pathogen causing pulmonary disease in immunocompetent patients. Little is known about the host defense against M. kansasii and its intracellular survival strategy inside macrophages. In the present study, we obtained six clinical isolates from patients with M. kansasii pulmonary disease and investigated the intracellular growth and cytotoxic effects of M. kansasii inside mouse bone marrow-derived macrophages (BMDM) as well as cytokine secretion from BMDM. Interestingly, two isolates, SM-1 and 2693-20, displayed faster growth rates and higher levels of TNF-α secretion from macrophages when compared to the other strains. In addition, SM-1 and 2693-20 also induced massive cell death in BMDM and THP-1 acute monocytic leukemia cells, while the slow growing strains induced significantly lower levels of cell death. This cytotoxicity was mainly caused by necrosis, not apoptosis and it was TNF-α-independent. Caspase inhibitors failed to block M. kansasii-induced macrophage death. In addition, necrosis caused by the fast growing strains was accompanied by the loss of mitochondrial membrane potential (ΔΨm). When dissipation of ΔΨm was inhibited by the classical mitochondrial permeability transition (MPT) inhibitor cyclosporine A (CsA), macrophage necrosis was reduced. These results suggest that clinical isolates of M. kansasii that grow faster in macrophages induce higher levels of necrosis in a ΔΨm loss-dependent manner.

Original languageEnglish
Pages (from-to)160-167
Number of pages8
JournalMicrobial Pathogenesis
Volume48
Issue number5
DOIs
Publication statusPublished - 2010 May 1

Fingerprint

Mycobacterium kansasii
Macrophages
Necrosis
Lung Diseases
Cell Death
Leukemia, Monocytic, Acute
Caspase Inhibitors
Mitochondrial Membrane Potential
Growth
Cyclosporine
Permeability
Apoptosis
Cytokines

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Infectious Diseases

Cite this

Sohn, H., Kim, K. W., Kang, H. B., Won, C. J., Kim, W. S., Lee, B., ... Kim, H. J. (2010). Induction of macrophage death by clinical strains of Mycobacterium kansasii. Microbial Pathogenesis, 48(5), 160-167. https://doi.org/10.1016/j.micpath.2010.02.005
Sohn, Hosung ; Kim, Kwang Wook ; Kang, Hyun Bae ; Won, Choul Jae ; Kim, Woo Sik ; Lee, Byungsoo ; Kwon, O. Jung ; Koh, Won Jung ; Shin, SungJae ; Kim, Hwa Jung. / Induction of macrophage death by clinical strains of Mycobacterium kansasii. In: Microbial Pathogenesis. 2010 ; Vol. 48, No. 5. pp. 160-167.
@article{e6c92b30b51745f386830c32a235e5fa,
title = "Induction of macrophage death by clinical strains of Mycobacterium kansasii",
abstract = "Mycobacterium kansasii is a facultative intracellular pathogen causing pulmonary disease in immunocompetent patients. Little is known about the host defense against M. kansasii and its intracellular survival strategy inside macrophages. In the present study, we obtained six clinical isolates from patients with M. kansasii pulmonary disease and investigated the intracellular growth and cytotoxic effects of M. kansasii inside mouse bone marrow-derived macrophages (BMDM) as well as cytokine secretion from BMDM. Interestingly, two isolates, SM-1 and 2693-20, displayed faster growth rates and higher levels of TNF-α secretion from macrophages when compared to the other strains. In addition, SM-1 and 2693-20 also induced massive cell death in BMDM and THP-1 acute monocytic leukemia cells, while the slow growing strains induced significantly lower levels of cell death. This cytotoxicity was mainly caused by necrosis, not apoptosis and it was TNF-α-independent. Caspase inhibitors failed to block M. kansasii-induced macrophage death. In addition, necrosis caused by the fast growing strains was accompanied by the loss of mitochondrial membrane potential (ΔΨm). When dissipation of ΔΨm was inhibited by the classical mitochondrial permeability transition (MPT) inhibitor cyclosporine A (CsA), macrophage necrosis was reduced. These results suggest that clinical isolates of M. kansasii that grow faster in macrophages induce higher levels of necrosis in a ΔΨm loss-dependent manner.",
author = "Hosung Sohn and Kim, {Kwang Wook} and Kang, {Hyun Bae} and Won, {Choul Jae} and Kim, {Woo Sik} and Byungsoo Lee and Kwon, {O. Jung} and Koh, {Won Jung} and SungJae Shin and Kim, {Hwa Jung}",
year = "2010",
month = "5",
day = "1",
doi = "10.1016/j.micpath.2010.02.005",
language = "English",
volume = "48",
pages = "160--167",
journal = "Microbial Pathogenesis",
issn = "0882-4010",
publisher = "Academic Press Inc.",
number = "5",

}

Sohn, H, Kim, KW, Kang, HB, Won, CJ, Kim, WS, Lee, B, Kwon, OJ, Koh, WJ, Shin, S & Kim, HJ 2010, 'Induction of macrophage death by clinical strains of Mycobacterium kansasii', Microbial Pathogenesis, vol. 48, no. 5, pp. 160-167. https://doi.org/10.1016/j.micpath.2010.02.005

Induction of macrophage death by clinical strains of Mycobacterium kansasii. / Sohn, Hosung; Kim, Kwang Wook; Kang, Hyun Bae; Won, Choul Jae; Kim, Woo Sik; Lee, Byungsoo; Kwon, O. Jung; Koh, Won Jung; Shin, SungJae; Kim, Hwa Jung.

In: Microbial Pathogenesis, Vol. 48, No. 5, 01.05.2010, p. 160-167.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Induction of macrophage death by clinical strains of Mycobacterium kansasii

AU - Sohn, Hosung

AU - Kim, Kwang Wook

AU - Kang, Hyun Bae

AU - Won, Choul Jae

AU - Kim, Woo Sik

AU - Lee, Byungsoo

AU - Kwon, O. Jung

AU - Koh, Won Jung

AU - Shin, SungJae

AU - Kim, Hwa Jung

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Mycobacterium kansasii is a facultative intracellular pathogen causing pulmonary disease in immunocompetent patients. Little is known about the host defense against M. kansasii and its intracellular survival strategy inside macrophages. In the present study, we obtained six clinical isolates from patients with M. kansasii pulmonary disease and investigated the intracellular growth and cytotoxic effects of M. kansasii inside mouse bone marrow-derived macrophages (BMDM) as well as cytokine secretion from BMDM. Interestingly, two isolates, SM-1 and 2693-20, displayed faster growth rates and higher levels of TNF-α secretion from macrophages when compared to the other strains. In addition, SM-1 and 2693-20 also induced massive cell death in BMDM and THP-1 acute monocytic leukemia cells, while the slow growing strains induced significantly lower levels of cell death. This cytotoxicity was mainly caused by necrosis, not apoptosis and it was TNF-α-independent. Caspase inhibitors failed to block M. kansasii-induced macrophage death. In addition, necrosis caused by the fast growing strains was accompanied by the loss of mitochondrial membrane potential (ΔΨm). When dissipation of ΔΨm was inhibited by the classical mitochondrial permeability transition (MPT) inhibitor cyclosporine A (CsA), macrophage necrosis was reduced. These results suggest that clinical isolates of M. kansasii that grow faster in macrophages induce higher levels of necrosis in a ΔΨm loss-dependent manner.

AB - Mycobacterium kansasii is a facultative intracellular pathogen causing pulmonary disease in immunocompetent patients. Little is known about the host defense against M. kansasii and its intracellular survival strategy inside macrophages. In the present study, we obtained six clinical isolates from patients with M. kansasii pulmonary disease and investigated the intracellular growth and cytotoxic effects of M. kansasii inside mouse bone marrow-derived macrophages (BMDM) as well as cytokine secretion from BMDM. Interestingly, two isolates, SM-1 and 2693-20, displayed faster growth rates and higher levels of TNF-α secretion from macrophages when compared to the other strains. In addition, SM-1 and 2693-20 also induced massive cell death in BMDM and THP-1 acute monocytic leukemia cells, while the slow growing strains induced significantly lower levels of cell death. This cytotoxicity was mainly caused by necrosis, not apoptosis and it was TNF-α-independent. Caspase inhibitors failed to block M. kansasii-induced macrophage death. In addition, necrosis caused by the fast growing strains was accompanied by the loss of mitochondrial membrane potential (ΔΨm). When dissipation of ΔΨm was inhibited by the classical mitochondrial permeability transition (MPT) inhibitor cyclosporine A (CsA), macrophage necrosis was reduced. These results suggest that clinical isolates of M. kansasii that grow faster in macrophages induce higher levels of necrosis in a ΔΨm loss-dependent manner.

UR - http://www.scopus.com/inward/record.url?scp=77952953736&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952953736&partnerID=8YFLogxK

U2 - 10.1016/j.micpath.2010.02.005

DO - 10.1016/j.micpath.2010.02.005

M3 - Article

C2 - 20211241

AN - SCOPUS:77952953736

VL - 48

SP - 160

EP - 167

JO - Microbial Pathogenesis

JF - Microbial Pathogenesis

SN - 0882-4010

IS - 5

ER -