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Interleukin-15 augments superoxide production and microbicidal activity of human monocytes against Candida albicans
N Vázquez1, T J Walsh, D Friedman
1Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract:
Interleukin-15 (IL-15) is a newly described cytokine that shares biological activities with IL-2. We report here results demonstrating the ability of IL-15 to enhance superoxide production and antifungal activity of human monocytes. After 18 and 48 h of treatment with IL-15, human elutriated monocytes manifested enhanced superoxide production in response to either phorbol myristate acetate or opsonized Candida albicans blastoconidia. Similar results were obtained when monocytes were treated with IL-2, but to a lesser extent. Combination studies with IL-15 and IL-2 showed no additive or synergistic effects. Following incubation of monocytes with IL-15 for 18 h, there was no significant increase in mRNA transcripts for components of the NADPH oxidase complex, p40-phox, p47-phox, and gp91-phox, suggesting a posttranscriptional modulation of enhanced superoxide production. Antibodies against the gamma chain of the IL-2 receptor and, to a lesser extent, against the beta chain partially abrogated the IL-15-mediated enhanced superoxide production. Additionally, human monocytes showed enhanced killing activity against C. albicans after 18 h of incubation with IL-15 or IL-2, but this treatment did not enhance the ability of these cells to phagocytose the organism. In addition, the enhanced fungicidal activity seen after 18 h of treatment was no longer detectable after 48 h of cytokine treatment. Culture supernatants from the IL-15-treated monocytes were assayed for the presence of other proinflammatory cytokines. IL-15 treatment did not induce the release of detectable levels of tumor necrosis factor alpha, IL-1beta, or IL-12. Our results indicate that IL-15 upregulates the microbicidal activity of human monocytes against C. albicans.
Insights
Interleukin-15 (IL-15) enhances human monocyte superoxide production and antifungal activity against Candida albicans. This cytokine boosts microbicidal capacity, suggesting a role in innate immunity.
Area of Science:
- Immunology
- Cell Biology
Background:
- Interleukin-15 (IL-15) is a cytokine with biological activities similar to Interleukin-2 (IL-2).
- Human monocytes play a crucial role in innate immunity, including the response to fungal pathogens like Candida albicans.
Purpose of the Study:
- To investigate the effects of IL-15 on human monocyte function, specifically superoxide production and antifungal activity.
- To compare the effects of IL-15 with IL-2 and explore potential synergistic interactions.
Main Methods:
- Human monocytes were treated with IL-15 and/or IL-2.
- Superoxide production was measured in response to phorbol myristate acetate and Candida albicans.
- Antifungal activity and phagocytosis were assessed.
- mRNA transcripts for NADPH oxidase components were analyzed.
- Antibodies against IL-2 receptor chains were used to investigate signaling pathways.
Main Results:
- IL-15 significantly enhanced superoxide production and antifungal activity of human monocytes against Candida albicans.
- These effects were observed after 18 hours of treatment and were comparable to, but not synergistic with, IL-2.
- Enhanced activity was not linked to increased mRNA levels of NADPH oxidase components, suggesting posttranscriptional regulation.
- IL-15 treatment did not enhance monocyte phagocytosis of Candida albicans.
- Antibodies against IL-2 receptor gamma and beta chains partially blocked IL-15's effects.
- Enhanced fungicidal activity diminished after 48 hours of IL-15 treatment.
Conclusions:
- IL-15 upregulates the microbicidal activity of human monocytes against Candida albicans.
- The mechanism involves enhanced superoxide production and fungicidal activity, potentially through posttranscriptional modulation and IL-2 receptor signaling.
- IL-15 represents a promising cytokine for bolstering innate immune responses against fungal infections.