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, Sung Jae 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

Bibliographical note

Funding Information:
This study was supported by the research fund of Chungnam National University (2008) and the Korea Science & Engineering Foundation (KOSEF) through the Infection Signaling Network Research Center (R13-2007-020-01000-0) at Chungnam National University.

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Infectious Diseases

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