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Infection and Immunity, February 2005, p. 770-777, Vol. 73, No. 2
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.2.770-777.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Enhanced Killing of Candida albicans by Human Macrophages Adherent to Type 1 Collagen Matrices via Induction of Phagolysosomal Fusion

Simon L. Newman,* Bindu Bhugra, Angela Holly, and Randal E. Morris

Division of Infectious Diseases, Department of Internal Medicine, and Department of Anatomy, Cell Biology, and Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio

Received 3 August 2004/ Returned for modification 31 August 2004/ Accepted 31 October 2004

Candida albicans, a component of the normal flora of the alimentary tract and mucocutaneous membranes, is the leading cause of invasive fungal disease in premature infants, diabetics, and surgical patients and of oropharyngeal disease in AIDS patients. As little is known about the regulation of monocyte/macrophage anti-Candida activity, we sought to determine if fungicidal activity might be regulated by extracellular matrix proteins to which monocytes/macrophages are adherent in vivo. Compared to monocyte/macrophages that adhered to plastic, human monocytes and monocyte-derived macrophages that adhered to type 1 collagen matrices, but not to fibronectin, vitronectin, or laminin, demonstrated a significant increase in candidacidal activity. The enhancement of monocyte fungicidal activity was maintained over a 4-h period, whereas macrophage fungicidal activity was maximum at 1 h. Although adherence of monocytes and macrophages to collagen matrices concomitantly enhanced the production of superoxide anion, only the fungicidal activity of collagen-adherent monocytes was partially blocked by superoxide dismutase and catalase. Remarkably, we found that only 10% of the phagosomes in C. albicans-infected macrophages that adhered to plastic fused with lysosomes. In contrast, 80% of yeast-containing phagosomes of collagen-adherent macrophages fused with lysosomes. These data suggest that nonoxidative mechanisms are critical for human macrophage anti-Candida activity and that C. albicans pathogenicity is mediated, in part, by its ability to inhibit phagolysosomal fusion in macrophages.

* Corresponding author. Mailing address: Division of Infectious Diseases, University of Cincinnati Col. Med., P.O. Box 670560, Cincinnati, OH 45267-0560. Phone: (513) 558-4709. Fax: (513) 558-2089. E-mail: newmansl{at}uc.edu.

Editor: T. R. Kozel

Infection and Immunity, February 2005, p. 770-777, Vol. 73, No. 2
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.2.770-777.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Marcil, A., Gadoury, C., Ash, J., Zhang, J., Nantel, A., Whiteway, M. (2008). Analysis of PRA1 and Its Relationship to Candida albicans- Macrophage Interactions. Infect. Immun. 76: 4345-4358 [Abstract] [Full Text]  
  • Newman, S. L., Gootee, L., Hilty, J., Morris, R. E. (2006). Human Macrophages Do Not Require Phagosome Acidification to Mediate Fungistatic/Fungicidal Activity against Histoplasma capsulatum. J. Immunol. 176: 1806-1813 [Abstract] [Full Text]  
  • Gildea, L. A., Ciraolo, G. M., Morris, R. E., Newman, S. L. (2005). Human Dendritic Cell Activity against Histoplasma capsulatum Is Mediated via Phagolysosomal Fusion. Infect. Immun. 73: 6803-6811 [Abstract] [Full Text]  


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