title: IFN-γ promotes THP-1 cell apoptosis during early infection with Mycobacterium bovis by activating different apoptotic signaling.
abstract: 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.
authors.affiliation: State Key Lab of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Jiaoer
authors.initials: J
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kouadir
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Deming
authors.initials: D
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D009163:Mycobacterium bovis / Q000276:immunology* / Q000472:pathogenicity; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation
chemical_list: D051033:Apoptosis Inducing Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D053148:Caspase 3; D053181:Caspase 8