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Support of Paracoccidioides brasiliensis multiplication by human monocytes or macrophages: inhibition by activated
M Moscardi-Bacchi1, E Brummer, D A Stevens
1Faculdade de Medicina, University of Estadual Paulista, Botucatu, Brazil.
Abstract:
The interaction of human monocytes or monocyte-derived macrophages and yeast-form Paracoccidioides brasiliensis was studied in vitro. Yeast cells were readily ingested by adherent monocytes or macrophages. Multiplication of P. brasiliensis, measured by growth as colony forming units (cfu) on a supplemented medium with good plating efficiency, was greater in monocyte co-cultures compared to the number of cfu obtained from complete tissue-culture medium (CTCM). Multiplication increased with time in macrophage co-cultures, e.g., from two-six-fold in 24 h to nine-fold in 72 h. Microscopic observations indicated that ingested yeast cells multiplied inside macrophages. When monocytes were treated with supernate cytokines (CK) from concanavalin-A-stimulated mononuclear cells, then co-cultured with P. brasiliensis, multiplication was significantly inhibited compared with control monocyte co-cultures. Treatment of macrophages--derived from monocytes by culture in vitro for 3 days--for a further 3 days with CK resulted in maximal inhibition of multiplication over the subsequent 72 h. Similarly, when monocyte-derived macrophages (after culture for 7 days) were treated for 3 days with recombinant human gamma-interferon (IFN; 300 U/ml) or CK they restricted multiplication of P. brasiliensis by 65% and 95%, respectively, compared with control macrophages. Antibody to IFN abrogated the effect of IFN or CK treatment. These findings show that ingested P. brasiliensis can multiply in human monocytes or macrophages and that this multiplication can be restricted by activated monocytes or macrophages.
Insights
Human monocytes and macrophages can be infected by Paracoccidioides brasiliensis yeast. Activated immune cells, like those treated with cytokines or gamma-interferon, can restrict fungal multiplication within these cells.
Area of Science:
- Immunology
- Mycology
- Cell Biology
Background:
- Paracoccidioides brasiliensis is a fungus that causes paracoccidioidomycosis.
- Human monocytes and macrophages are key immune cells involved in combating fungal infections.
- Understanding the interaction between these cells and the fungus is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the in vitro interaction between human monocytes/macrophages and yeast-form P. brasiliensis.
- To determine if P. brasiliensis multiplies within these host cells.
- To assess the role of cytokines and gamma-interferon in controlling P. brasiliensis proliferation.
Main Methods:
- Co-culture of human monocytes or monocyte-derived macrophages with yeast-form P. brasiliensis.
- Quantification of P. brasiliensis growth using colony-forming units (CFUs).
- Treatment of immune cells with cytokines (CK) or recombinant human gamma-interferon (IFN) prior to or during co-culture.
Main Results:
- Yeast-form P. brasiliensis readily ingested by monocytes and macrophages.
- Significant multiplication of P. brasiliensis observed within monocytes and macrophages over time.
- Pre-treatment with cytokines or gamma-interferon significantly inhibited P. brasiliensis multiplication.
- Antibody to gamma-interferon abrogated the inhibitory effects.
Conclusions:
- Human monocytes and macrophages support the multiplication of yeast-form P. brasiliensis.
- Activated monocytes and macrophages, particularly when treated with cytokines or gamma-interferon, can restrict fungal growth.
- These findings highlight the potential of immune cell activation as a therapeutic strategy against paracoccidioidomycosis.