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Journal Article | Research Support, Non-U.S. Gov't

Tumor necrosis factor-inducing activities of Cryptococcus neoformans components.

D Delfino, L Cianci, M Migliardo, G Mancuso, V Cusumano, C Corradini, G Teti
D Delfino
Istituto di Microbiologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Messina, Italy.
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L Cianci
Istituto di Microbiologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Messina, Italy.
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M Migliardo
Istituto di Microbiologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Messina, Italy.
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G Mancuso
Istituto di Microbiologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Messina, Italy.
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V Cusumano
Istituto di Microbiologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Messina, Italy.
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C Corradini
Istituto di Microbiologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Messina, Italy.
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G Teti
Istituto di Microbiologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Messina, Italy.
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ABSTRACT

Cryptococcus neoformans-induced tumor necrosis factor alpha (TNF-alpha) production may lead to increased human immunodeficiency virus replication in patients with AIDS. In order to identify cryptococcal components that are predominantly responsible for stimulating TNF production, various concentrations of glucuronoxylomannan (GXM), galactoxylomannan (GalXM), mannoproteins (MP), and alpha(1-3) [corrected] glucan were added to whole-blood cultures. All of the cryptococcal components tested, as well as whole heat-killed cryptococci, were capable of inducing TNF-alpha release in a dose-dependent manner. MP were significantly more potent than any of the other cryptococcal components tested or heat-killed cryptococci in stimulating TNF-alpha production (P < 0.05). GXM, in contrast, was significantly less potent in this activity than either GalXM or MP (P < 0.05). As little as 0.5 microg of MP per ml was sufficient to produce moderate but significant elevations of TNF-alpha release. Maximal MP-induced TNF-alpha levels were similar to those induced by Salmonella enteritidis lipopolysaccharide, our positive control. Further experiments using isolated leukocytes suggested that monocytes were the cell population mainly responsible for TNF-alpha production, although the participation of other cell types could not be excluded. The presence of complement-sufficient plasma was a necessary requirement for TNF-alpha induction by GXM, GalXM, and low doses of MP. High MP concentrations (100 microg/ml) were also capable of stimulating TNF-alpha production in the absence of plasma. These data indicate that soluble products released by C. neoformans are capable of inducing TNF-alpha secretion in human leukocytes. This may be clinically relevant, since high concentrations of such products are frequently found in the body fluids of AIDS patients infected with C. neoformans.

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Tumor necrosis factor-inducing activities of Cryptococcus neoformans components.
D Delfino, L Cianci, M Migliardo, G Mancuso, V Cusumano, C Corradini, G Teti
Infection and Immunity Dec 1996, 64 (12) 5199-5204; DOI:

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Tumor necrosis factor-inducing activities of Cryptococcus neoformans components.
D Delfino, L Cianci, M Migliardo, G Mancuso, V Cusumano, C Corradini, G Teti
Infection and Immunity Dec 1996, 64 (12) 5199-5204; DOI:
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