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Tumor necrosis factor-inducing activities of Cryptococcus neoformans components
D Delfino1, L Cianci, M Migliardo
1Istituto di Microbiologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Messina, Italy.
Infection and Immunity
|December 1, 1996
Summary
Cryptococcus neoformans mannoproteins (MP) strongly stimulate tumor necrosis factor alpha (TNF-alpha) release, potentially increasing HIV replication in AIDS patients. Other cryptococcal components also induce TNF-alpha, but less potently than MP.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Cryptococcus neoformans infection is a significant concern for patients with Acquired Immunodeficiency Syndrome (AIDS).
- Tumor necrosis factor alpha (TNF-alpha) production may exacerbate human immunodeficiency virus (HIV) replication in AIDS patients.
- Identifying specific cryptococcal components that stimulate TNF-alpha is crucial for understanding disease pathogenesis.
Purpose of the Study:
- To determine which components of Cryptococcus neoformans are primarily responsible for stimulating TNF-alpha production.
- To investigate the dose-dependent effects of various cryptococcal components on TNF-alpha release.
- To identify the immune cells involved in TNF-alpha production and the role of plasma in this process.
Main Methods:
- Whole-blood cultures were stimulated with varying concentrations of glucuronoxylomannan (GXM), galactoxylomannan (GalXM), mannoproteins (MP), and alpha(1-3) glucan.
- TNF-alpha levels were measured in response to cryptococcal components and whole heat-killed cryptococci.
- Experiments using isolated leukocytes and complement-sufficient/deficient plasma were conducted to elucidate cellular and plasma requirements.
Main Results:
- All tested cryptococcal components, including MP, GXM, and GalXM, induced TNF-alpha release in a dose-dependent manner.
- Mannoproteins (MP) were significantly more potent stimulators of TNF-alpha production compared to other components and whole yeast cells.
- Monocytes were identified as the primary cell type responsible for TNF-alpha production, with plasma being essential for induction by GXM, GalXM, and low-dose MP.
Conclusions:
- Soluble products from Cryptococcus neoformans, particularly mannoproteins, can induce TNF-alpha secretion in human leukocytes.
- The potent induction of TNF-alpha by MP may have clinical implications for HIV replication in AIDS patients with cryptococcal infections.
- Understanding these interactions is vital for managing co-infections in immunocompromised individuals.