title: Chlamydia pneumoniae induces T cell apoptosis through glutathione redox imbalance and secretion of TNF-alpha.
abstract: Chlamydia pneumoniae persistent infection has been implicated in the pathogenesis of several chronic inflammatory diseases including atherosclerosis, and we hypothesized that modulation of the apoptosis of macrophages and/or T cells by C. pneumoniae infection may contribute to the development of such diseases. We therefore evaluated apoptosis, cytokine response, and redox status in human primary T cells and macrophages infected with C. pneumoniae. In addition, co-cultures of T cells and macrophages infected with C. pneumoniae were also carried out. Apoptosis, and levels of glutathione (GSH), glutathione disulfide (GSSG), and tumour necrosis factor (TNF)-alpha were measured by flow cytometry, high performance liquid chromatography and enzyme-linked immunosorbent assay. C. pneumoniae induced apoptosis in T cells as well as in co-cultures of T cells and infected macrophages by marked decrease in GSH/GSSG ratio and increased production of TNF-alpha, respectively. The results demonstrate that interaction of C. pneumoniae with T cells and/or macrophages characterized by interference with redox status, and secretion of tumour necrosis factor-alpha culminates in the induction of T cell apoptosis and survival of infected macrophages. In conclusion, the inappropriate T cell response against C. pneumoniae and survival of infected macrophages could explain the persistence of this intracellular obligate pathogen in the host-organism; it may contribute to the development of chronic inflammatory diseases, although further studies are needed to clarify such a complex mechanism.
authors.affiliation: Department of Public Health Sciences, Sapienza University, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Sessa
authors.forename: M
authors.initials: M
authors.lastname: Di Pietro
authors.forename: G
authors.initials: G
authors.lastname: Schiavoni
authors.forename: A
authors.initials: A
authors.lastname: Macone
authors.forename: B
authors.initials: B
authors.lastname: Maras
authors.forename: M
authors.initials: M
authors.lastname: Fontana
authors.forename: C
authors.initials: C
authors.lastname: Zagaglia
authors.forename: M
authors.initials: M
authors.lastname: Nicoletti
authors.forename: M
authors.initials: M
authors.lastname: Del Piano
authors.forename: S
authors.initials: S
authors.lastname: Morrone
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D002851:Chromatography, High Pressure Liquid; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D010084:Oxidation-Reduction; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014409:Tumor Necrosis Factor-alpha; D005978:Glutathione; D019803:Glutathione Disulfide