Open AccessIFN‐γ promotes THP‐1 cell apoptosis during early infection with Mycobacterium bovis by activating different apoptotic signaling
Author(s) -
Zhang Jiaoer,
Sun Bin,
Huang Ying,
Kouadir Mohammed,
Zhou Xiangmei,
Wang Yang,
Zhao Deming
Publication year - 2010
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2010.00732.x
Subject(s) - apoptosis , biology , tumor necrosis factor alpha , mycobacterium bovis , thp1 cell line , microbiology and biotechnology , interferon , programmed cell death , immune system , multiplicity of infection , caspase , cell culture , immunology , medicine , mycobacterium tuberculosis , biochemistry , virus , tuberculosis , pathology , genetics
Macrophage apoptosis represents an important innate defense mechanism against intracellular mycobacterial infection. Previous publications have shown that interferon‐γ (IFN‐γ) is involved in apoptosis of immune cells infected with mycobacteria. In this study, the impact of IFN‐γ treatment on phorbol‐12‐myristate‐13‐acetate‐differentiated THP‐1 cells infected with Mycobacterium bovis was investigated. The results showed that IFN‐γ increased apoptosis of THP‐1 cells infected with M. bovis at a low multiplicity of infection (MOI) in a time‐dependent manner. The percentage of cells undergoing apoptosis in IFN‐γ‐treated THP‐1 cells increased from 4.3% at 12 h to 36.5% at 72 h upon infection with an MOI of 10. Activation of caspases‐3 and ‐8 increased 8.3‐ and 6.7‐fold, respectively. Neutralizing endogenous tumor necrosis factor‐α (TNF‐α) significantly inhibited IFN‐γ‐induced apoptosis of M. bovis ‐infected THP‐1 cells. No significant change in IFN‐γ‐induced apoptosis was observed in M. bovis ‐infected cells after the addition of c‐Jun N‐terminal kinase and NF‐κB pathways' inhibitors. Translocation of apoptosis‐inducing factor (AIF) to the nucleus of M. bovis ‐infected THP‐1 cells was observed in 23.4% of IFN‐γ‐treated cells, compared with 11.0% in untreated cells. Taken together, these results suggest that IFN‐γ promotes apoptosis of M. bovis ‐infected THP‐1 cells during early infection through the TNF‐α‐mediated death receptor and the AIF apoptotic pathway.