title: Penicillium marneffei causes osteopontin-mediated production of interleukin-12 by peripheral blood mononuclear cells.
abstract: We investigated the role of osteopontin (OPN) in interleukin-12 (IL-12) production from peripheral blood mononuclear cells (PBMCs) stimulated with Penicillium marneffei. Kinetic studies showed that OPN synthesis preceded that of IL-12 at both mRNA and protein levels when PBMCs were cocultured with P. marneffei. Treatment with anti-OPN monoclonal antibodies (MAb) significantly suppressed IL-12 secretion. Furthermore, native OPN induced a profound level of synthesis of IL-12 from noninfected PBMCs. The major cellular source of OPN was monocytes, because depletion of CD14(+) cells resulted in the abrogation of such production. We also examined the regulatory role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in OPN secretion from P. marneffei-stimulated PBMCs. Neutralizing anti-GM-CSF MAb significantly reduced OPN secretion, and treatment with this cytokine induced OPN production from both infected and noninfected PBMCs. Finally, antagonists against the mannose receptor but not the beta-glucan receptor almost completely abrogated the production of OPN. Our results demonstrated that OPN secreted from monocytes is involved in the production of IL-12 from PBMCs after stimulation with P. marneffei and that OPN production is regulated by GM-CSF. Our results also indicated the possible involvement of the mannose receptor as a signal-transducing receptor for triggering the secretion of OPN by P. marneffei-stimulated PBMCs.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Koguchi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Segawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Maeda
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Uede
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000209:etiology; D018920:Coculture Techniques; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009000:Monocytes / Q000276:immunology; D053495:Osteopontin; D010407:Penicillium / Q000276:immunology* / Q000472:pathogenicity; D021122:Protein Subunits; D011956:Receptors, Cell Surface / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology
chemical_list: D053762:Interleukin-12 Subunit p40; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D021122:Protein Subunits; D011956:Receptors, Cell Surface; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor