Interleukin-15 augments superoxide production and microbicidal activity of human monocytes against Candida albicans.
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.
Vázquez
N
N
Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Walsh
T J
TJ
Friedman
D
D
Chanock
S J
SJ
Lyman
C A
CA
D002176:Candida albicans / Q000276:immunology*; D017077:Culture Media, Conditioned / Q000032:analysis; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D019409:Interleukin-15 / Q000276:immunology* / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D009500:Neutralization Tests; D010587:Phagocytosis / Q000276:immunology; D010750:Phosphoproteins / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000276:immunology; D016897:Respiratory Burst / Q000276:immunology; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017077:Culture Media, Conditioned; D007375:Interleukin-1; D019409:Interleukin-15; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; C085072:neutrophil cytosol factor 40K; D013481:Superoxides; D018664:Interleukin-12; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D013755:Tetradecanoylphorbol Acetate