title: Chlamydia pneumoniae inhibits apoptosis in human peripheral blood mononuclear cells through induction of IL-10.
abstract: Chlamydia pneumoniae is a common cause of pulmonary infection, with serum positivity in at least 50% of the general population. In this study, we report that human PBMCs exposed to C. pneumoniae are resistant to apoptosis induced by the potent photoactivated chemotherapeutic agents 8-methoxypsoralen and hypericin. In contrast, PBMCs treated with a heat-inactivated inoculum exhibit normal susceptibility to apoptosis. We also observed that human PBMCs are responsive to C. pneumoniae infection by secretion of key immune regulatory cytokines, including IL-12 and IL-10. While IL-12 may play an important role in limiting C. pneumoniae proliferation within cells, IL-10 serves an anti-inflammatory function by down-regulating proinflammatory cytokines such as IL-12 and TNF-alpha. Depletion of endogenous IL-10, but not of IL-12, abolished the apoptosis resistance of C. pneumoniae-infected PBMCs. Furthermore, addition of exogenous IL-10, but not IL-12, significantly increased the resistance of control inoculum-treated PBMCs to photoactivated 8-methoxypsoralen- and hypericin-induced apoptosis. Therefore, we conclude that C. pneumoniae possesses an antiapoptotic mechanism. The resistance to apoptosis observed in PBMCs exposed to C. pneumoniae is due, at least partially, to the IL-10 induced during C. pneumoniae infection.
authors.affiliation: Departments of Dermatology and Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Geng
authors.forename: R B
authors.initials: RB
authors.lastname: Shane
authors.forename: K
authors.initials: K
authors.lastname: Berencsi
authors.forename: E
authors.initials: E
authors.lastname: Gonczol
authors.forename: M H
authors.initials: MH
authors.lastname: Zaki
authors.forename: D J
authors.initials: DJ
authors.lastname: Margolis
authors.forename: G
authors.initials: G
authors.lastname: Trinchieri
authors.forename: A H
authors.initials: AH
authors.lastname: Rook
mesh_terms: D000873:Anthracenes; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D008730:Methoxsalen / Q000494:pharmacology; D010569:Perylene / Q000031:analogs & derivatives / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D000873:Anthracenes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D010569:Perylene; C004965:hypericin; D008730:Methoxsalen