title: Divergent modulation of Chlamydia pneumoniae infection cycle in human monocytic and endothelial cells by iron, tryptophan availability and interferon gamma.
abstract: Chlamydia pneumoniae is an obligatory intracellular bacterium causing chronic inflammatory diseases in humans. We studied the role of the nutritive factors, iron and tryptophan, towards the course of infection and immune response pathways in C. pneumoniae infected endothelial cells and monocytes. Human endothelial (EA.hy923) and monocytic cells (THP-1) were infected with C. pneumoniae, supplemented with iron or 1-methyltryptophan (1-MT), an inhibitor of the tryptophan degrading enzyme indoleamine 2,3-dioxygenase (IDO), and subsequently stimulated with IFN-gamma or left untreated. The number of infected cells, the morphology and quantity of C. pneumoniae inclusion bodies, IDO activity and innate immune effector pathways were analysed. While neither iron challenge, IDO inhibition or IFN-gamma treatment had a significant effect on C. pneumoniae morphology or numbers within THP-1 monocytic cells, iron supplementation to EA.hy926 cells resulted in promotion of C. pneumoniae proliferation and differentiation while IFN-gamma had an inhibitory effect. Furthermore, the number of infected endothelial cells was significantly decreased upon 1-MT treatment. C. pneumoniae infection induced a pro-inflammatory immune response as evidenced by increased IDO activity, neopterin formation or TNF-alpha production in THP-1 but not in endothelial cells. These pathways were superinduced upon IFN-gamma treatment and partly modulated by iron supplementation. Our results demonstrate that the infectious cycle of C. pneumoniae behaves differently between monocytic and endothelial cells. While the intracellular pathogen remains in a persistent form within monocytes, it can differentiate and proliferate within endothelial cells indicating that endothelial cells are a preferred environment for Chlamydia. Nutritive factors such as iron have subtle effects on C. pneumoniae biology in endothelial, but not monocytic cells. Our results contribute to a better understanding of C. pneumoniae infection and its role in chronic inflammatory diseases such as atherosclerosis.
authors.affiliation: Department of Internal Medicine I, Clinical Immunology and Infectious Diseases, Innsbruck, Austria.
authors.forename: Rosa
authors.initials: R
authors.lastname: Bellmann-Weiler
authors.forename: Verena
authors.initials: V
authors.lastname: Martinz
authors.forename: Katharina
authors.initials: K
authors.lastname: Kurz
authors.forename: Sabine
authors.initials: S
authors.lastname: Engl
authors.forename: Clemens
authors.initials: C
authors.lastname: Feistritzer
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.forename: Jan
authors.initials: J
authors.lastname: Rupp
authors.forename: Mika
authors.initials: M
authors.lastname: Paldanius
authors.forename: Guenter
authors.initials: G
authors.lastname: Weiss
mesh_terms: D048708:Cell Growth Processes / Q000187:drug effects; D002460:Cell Line; D023521:Chlamydophila Infections / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology*; D016993:Chlamydophila pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D045586:Intranuclear Inclusion Bodies / Q000473:pathology; D007501:Iron / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D014364:Tryptophan; D007501:Iron; C525396:1-methyltryptophan