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

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 mono...

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Bibliographic Details
Published in:Infection and Immunity 2005-02, Vol.73 (2), p.770-777
Main Authors: Newman, Simon L, Bhugra, Bindu, Holly, Angela, Morris, Randal E
Format: Article
Language:English
Subjects:
Biological and medical sciences
Candida albicans
Candida albicans - immunology
Candidiasis - immunology
Cell Adhesion - immunology
Collagen Type I - immunology
Fibronectins - immunology
Fundamental and applied biological sciences. Psychology
Fungal and Parasitic Infections
Humans
Laminin - immunology
Macrophages - immunology
Microbiology
Miscellaneous
Mycology
Phagosomes - immunology
Time Factors
Vitronectin - immunology
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Summary: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.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.73.2.770-777.2005