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Infection and Immunity, April 2006, p. 2415-2422, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2415-2422.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Spherules Derived from Coccidioides posadasii Promote Human Dendritic Cell Maturation and Activation

Sara O. Dionne,1,2,3 Abigail B. Podany,2 Yvette W. Ruiz,1,3,{dagger} Neil M. Ampel,1,2,4 John N. Galgiani,1,4 and Douglas F. Lake1,2,3*

Valley Fever Center for Excellence,1 Department of Microbiology and Immunology,2 Arizona Cancer Center,3 Department of Medicine and Medical and Research Services, Southern Arizona Veterans Affairs Medical Center, Tucson, Arizona4

Received 27 October 2005/ Returned for modification 3 December 2005/ Accepted 11 January 2006

Previous studies have shown that dendritic cells (DC) pulsed with T27K, an antigenic preparation derived from spherules (of Coccidioides posadasii), activate peripheral blood mononuclear cells (PBMC) from nonimmune subjects as well as from patients with disseminated coccidioidomycosis. In this study, we have assessed the interaction between human DC and C. posadasii spherules in order to better understand the initial response between Coccidioides and the human host. Whole autoclaved spherules induced lymphocyte transformation in PBMC obtained from immune but not from nonimmune donors. Immature DC (iDC) bound fluorescein isothiocyanate-labeled spherules in a time- and temperature-dependent manner. This binding was blocked by the addition of mannan, suggesting mannose receptor involvement in the DC-Coccidioides interaction. Binding was subsequently associated with ingestion and intracellular processing of spherules. Coculturing of spherules with iDC was associated with the development of mature DC that were morphologically, phenotypically, and functionally similar to those induced by tumor necrosis factor alpha and prostaglandin E2. Finally, spherules incubated with iDC induced activation of PBMC from nonimmune donors. These data indicate that human DC are capable of binding, internalizing, and presenting antigens from Coccidioides spherules and suggest that DC may play a critical early role in the formation of a cellular immune response in human coccidioidomycosis.

* Corresponding author. Present address: Center for Innovations in Medicine, The Biodesign Institute, School of Life Sciences, Room B224B, Arizona State University, 1001 S. McAllister Ave., Tempe, AZ 85287. Phone: (480) 727-9579. Fax: (480) 727-0756. E-mail: Douglas.Lake{at}asu.edu.

Editor: A. Casadevall

{dagger} Present address: Center for Innovations in Medicine, The Biodesign Institute, Arizona State University, Tempe, AZ 85287.

Infection and Immunity, April 2006, p. 2415-2422, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2415-2422.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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