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Infection and Immunity, August 2001, p. 5115-5120, Vol. 69, No. 8
Laboratory of Cell Regulation and
Carcinogenesis,1 Immunocompromised Host
Section, Pediatric Oncology Branch,2 and
Advanced Technology Center,3 National
Cancer Institute, National Institutes of Health, Bethesda, Maryland
20892
Received 30 November 2000/Returned for modification 6 February
2001/Accepted 17 April 2001
Candida albicans is an opportunistic fungal pathogen
and a major cause of morbidity and mortality in patients with
compromised immune function. The cytokine response to tissue invasion
by C. albicans can influence the differentiation and
function of lymphocytes and other mononuclear cells that are critical
components of the host response. While the production of transforming
growth factor
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.8.5115-5120.2001
Invasive Candidiasis Stimulates Hepatocyte and
Monocyte Production of Active Transforming Growth Factor
(TGF-) has been documented in mice infected with
C. albicans and is known to suppress phagocyte function,
the cellular source and role of this cytokine in the pathogenesis of
systemic candidiasis are not well understood. We have investigated the
source of production of TGF- by immunohistochemical studies in
tissue samples from patients with an uncommon complication of
lymphoreticular malignancy, chronic disseminated candidiasis (CDC), and
from a neutropenic-rabbit model of CDC. Liver biopsy specimens from
patients with documented CDC demonstrated intense staining for
extracellular matrix-associated TGF-1 within inflammatory
granulomas, as well as staining for TGF-1 and TGF-3 within
adjacent hepatocytes. These results correlate with the
immunolocalization of TGF- observed in livers of infected neutropenic rabbits, using a neutralizing antibody that recognizes the
mature TGF- protein. Human peripheral blood monocytes incubated with
C. albicans in vitro release large amounts of biologically active TGF-1. The data demonstrate that local production of active TGF-s by hepatocytes and by infected mononuclear cells is a
component of the response to C. albicans infection that
most probably contributes to disease progression in the
immunocompromised host.
*
Corresponding author. Mailing address:
Immunocompromised Host Section, Pediatric Oncology Branch and The
Advanced Technology Center, National Cancer Institute, 8717 Grovemont
Circle, Gaithersburg, MD 20877. Phone: (301) 435-7559. Fax: (301)
402-3134. E-mail: sc83a{at}nih.gov.
Infection and Immunity, August 2001, p. 5115-5120, Vol. 69, No. 8
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.8.5115-5120.2001
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