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Infection and Immunity, November 2001, p. 6813-6822, Vol. 69, No. 11
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.11.6813-6822.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Candida albicans Is Phagocytosed,
Killed, and Processed for Antigen Presentation by Human Dendritic
Cells
Simon L.
Newman* and
Angela
Holly
Department of Internal Medicine, Division of
Infectious Diseases, University of Cincinnati College of Medicine,
Cincinnati, Ohio 45267
Received 22 March 2001/Returned for modification 25 May
2001/Accepted 13 August 2001
Candida albicans is a component of the normal flora
of the alimentary tract and also is found on the mucocutaneous
membranes of the healthy host. Candida is the leading
cause of invasive fungal disease in premature infants, diabetics, and
surgical patients, and of oropharyngeal disease in AIDS patients. As
the induction of cell-mediated immunity to Candida is of
critical importance in host defense, we sought to determine
whether human dendritic cells (DC) could phagocytose and degrade
Candida and subsequently present Candida
antigens to T cells. Immature DC obtained by culture of human monocytes
in the presence of granulocyte-macrophage colony-stimulating factor and
interleukin-4 phagocytosed unopsonized Candida in a time-dependent manner, and phagocytosis was not enhanced by
opsonization of Candida in serum. Like macrophages
(M
), DC recognized Candida by the mannose-fucose
receptor. Upon ingestion, DC killed Candida as
efficiently as human M
, and fungicidal activity was not enhanced by
the presence of fresh serum. Although phagocytosis of
Candida by DC stimulated the production of superoxide
anion, inhibitors of the respiratory burst (or NO production) did not
inhibit killing of Candida, even when phagocytosis was
blocked by preincubation of DC with cytochalasin D. Further, although
apparently only modest phagolysosomal fusion occurred upon DC
phagocytosis of Candida, killing of
Candida under anaerobic conditions was almost equivalent to killing under aerobic conditions. Finally, DC stimulated
Candida-specific lymphocyte proliferation in a
concentration-dependent manner after phagocytosis of both viable and
heat-killed Candida cells. These data suggest that, in
vivo, such interactions between DC and C. albicans may
facilitate the induction of cell-mediated immunity.
*
Corresponding author. Mailing address: Division of
Infectious Diseases, University of Cincinnati College of Medicine, P.O. Box 670560, Cincinnati, OH 45267-0560. Phone: (513) 558-4709. Fax:
(513) 558-2089. E-mail: newmansl{at}emailuc.edu.
Infection and Immunity, November 2001, p. 6813-6822, Vol. 69, No. 11
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.11.6813-6822.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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