title: Modulation of the antilisterial activity of human blood-derived macrophages by activating and deactivating cytokines.
abstract: A concept of macrophage deactivation by hormones and cytokines that opposes activation was recently proposed. Deactivation of the antilisterial activity of macrophages by IL-4, IL-10, and TGF-beta, as well as by dexamethasone, was studied here. IL-4, IL-10, and dexamethasone, but not TGF-beta, caused a complete loss of the competence of human blood-derived macrophages infected with Listeria monocytogenes to control or eliminate ingested bacteria. IL-10 and, to a lesser degree, dexamethasone lessened in parallel the capacity of macrophages to secrete H2O2. The antilisterial activity of cells simultaneously exposed to deactivating agents could be significantly augmented by IFN-gamma. Likewise, TNF-alpha and to a limited degree GM-CSF increased the antilisterial activity of cells treated with IL-10 and dexamethasone but not that of cells treated with IL-4. Suppression of TNF-alpha secretion in response to Listeria by TGF-beta, IL-10, dexamethasone, or pentoxifylline did not closely parallel antilisterial activity. Studies by transmission electron microscopy and actin staining suggested that deactivation by IL-10, IL-4, and dexamethasone of human blood-derived macrophages resulted in intraphagosomal multiplication of Listeria followed only then by an escape of bacteria into the cytoplasm. The antibacterial competence of human macrophages is lessened by IL-4 and IL-10 and augmented by IFN-gamma, TNF-alpha, and GM-CSF. The success of human macrophages in controlling intracellular pathogens appears to depend on the balance of activating and deactivating mediators modulating their activity.
authors.affiliation: Department of Medicine, University of Zürich, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Bläuer
authors.forename: P
authors.initials: P
authors.lastname: Groscurth
authors.forename: M
authors.initials: M
authors.lastname: Schneemann
authors.forename: G
authors.initials: G
authors.lastname: Schoedon
authors.forename: A
authors.initials: A
authors.lastname: Schaffner
mesh_terms: D016207:Cytokines / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008087:Listeria / Q000187:drug effects / Q000276:immunology*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D010587:Phagocytosis / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D016897:Respiratory Burst / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D003907:Dexamethasone; D007371:Interferon-gamma