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Infection and Immunity, May 2007, p. 2612-2620, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01841-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Interaction of Candida albicans with Adherent Human Peripheral Blood Mononuclear Cells Increases C. albicans Biofilm Formation and Results in Differential Expression of Pro- and Anti-Inflammatory Cytokines ^,

Jyotsna Chandra,^1,2 Thomas S. McCormick,² Yoshifumi Imamura,^1,2 Pranab K. Mukherjee,^1,2 and Mahmoud A. Ghannoum^1,2*

Center for Medical Mycology, University Hospitals Case Medical Center,¹ Department of Dermatology, Case Western Reserve University, 11100 Euclid Ave., Cleveland, Ohio 44106-5028²

Received 21 November 2006/ Returned for modification 13 December 2006/ Accepted 22 February 2007

Monocytes and macrophages are the cell types most commonly associated with the innate immune response against Candida albicans infection. Interactions between the host immune system and Candida organisms have been investigated for planktonic Candida cells, but no studies have addressed these interactions in a biofilm environment. In this study, for the first time, we evaluated the ability of C. albicans to form biofilms in the presence or absence of adherent peripheral blood mononuclear cells (PBMCs; enriched for monocytes and macrophages by adherence). Our analyses using scanning electron and confocal scanning laser microscopy showed that the presence of PBMCs enhanced the ability of C. albicans to form biofilms and that the majority of PBMCs were localized to the basal and middle layers of the biofilm. In contrast to the interactions of PBMCs with planktonic C. albicans, where PBMCs phagocytose fungal cells, PBMCs did not appear to phagocytose fungal cells in biofilms. Furthermore, time-lapse laser microscopy revealed dynamic interactions between C. albicans and PBMCs in a biofilm. Additionally, we found that (i) only viable PBMCs influence Candida biofilm formation, (ii) cell surface components of PBMCs did not contribute to the enhancement of C. albicans biofilm, (iii) the biofilm-enhancing effect of PBMCs is mediated by a soluble factor released into the coculture medium of PBMCs with C. albicans, and (iv) supernatant collected from this coculture contained differential levels of pro- and anti-inflammatory cytokines. Our studies provide new insight into the interaction between Candida biofilm and host immune cells and demonstrate that immunocytes may influence the ability of C. albicans to form biofilms.

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* Corresponding author. Mailing address: Center for Medical Mycology, Department of Dermatology, University Hospitals of Cleveland and Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5028. Phone: (216) 844-8580. Fax: (216) 844-1076. E-mail: Mahmoud.ghannoum{at}case.edu

Published ahead of print on 5 March 2007.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. Casadevall

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Infection and Immunity, May 2007, p. 2612-2620, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01841-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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