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Infection and Immunity, March 2002, p. 1042-1048, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1042-1048.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Penicillium marneffei Causes Osteopontin-Mediated Production of Interleukin-12 by Peripheral Blood Mononuclear Cells

Yoshinobu Koguchi,1 Kazuyoshi Kawakami,1* Shigeyuki Kon,2 Tatsuya Segawa,3 Masahiro Maeda,3 Toshimitsu Uede,2 and Atsushi Saito1

First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 Division of Molecular Immunology, Research Section of Molecular Pathogenesis, Institute for Genetic Medicine, Hokkaido University, Sapporo,2 Immuno-Biological Laboratories Co., Ltd., Gunma, Japan3

Received 15 June 2001/ Returned for modification 15 August 2001/ Accepted 1 November 2001

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 ß-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.

* Corresponding author. Mailing address: First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. Phone: 81 (98) 895-1144. Fax: 81 (98) 895-1414. E-mail: kawakami{at}med.u-ryukyu.ac.jp.

Infection and Immunity, March 2002, p. 1042-1048, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1042-1048.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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