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Infect Immun, June 1998, p. 2640-2647, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Interleukin-15 Activates Proinflammatory and Antimicrobial Functions in Polymorphonuclear Cells

Tiziana Musso,1,* Liliana Calosso,2 Mario Zucca,3 Maura Millesimo,1 Manuela Puliti,4 Silvia Bulfone-Paus,5 Chiara Merlino,1 Dianella Savoia,3 Rossana Cavallo,1 Alessandro Negro Ponzi,1 and Raffaele Badolato6

Department of Public Health and Microbiology,1 Postgraduate School of Clinical Pathology, Department of Genetics, Biology and Medical Chemistry,2 and Department of Clinical and Biological Sciences,3 University of Turin, Turin, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia,4 and Department of Pediatrics, University of Brescia, Brescia,6 Italy, and Institute of Immunology, Benjamin Franklin Medical Center, Free University, Berlin, Germany5

Received 3 November 1997/Returned for modification 8 December 1997/Accepted 13 March 1998

Interleukin-15 (IL-15) is a recently discovered cytokine produced by a wide range of different cell types including fibroblasts, keratinocytes, endothelial cells, and macrophages in response to lipopolysaccharide or microbial infection. This suggests that IL-15 may play a crucial role in the activation of phagocytic cells against pathogens. We studied polymorphonuclear leukocyte (PMN) activation by IL-15, evaluated as enhancement of PMN anti-Candida activity as well as IL-8 production, following stimulation with the cytokine. The PMN response to IL-15 depends on binding to the IL-15 receptor. Our experiments show that binding of a biotinylated human IL-15-immunoglobulin G2b IgG2b fusion protein was competed by the addition of human recombinant IL-15 (rIL-15) or of human rIL-2, suggesting that IL-15 binding to PMN might involve the IL-2Rbeta and IL-2Rgamma chains, which have been shown to be constitutively expressed by PMN. In addition, we show by reverse transcription-PCR and by flow cytometry with a specific anti-IL-15Ralpha chain monoclonal antibody that PMN express the IL-15Ralpha chain at the mRNA and protein levels. Incubation with IL-15 activated PMN to secrete the chemotactic factor IL-8, and the amount secreted was increased by costimulation with heat-inactivated Candida albicans. In addition, IL-15 primed the metabolic burst of PMN in response to formyl-methionyl-leucyl-phenylalanine but was not sufficient to trigger the respiratory burst or to increase the production of superoxide in PMN exposed to C. albicans. IL-15 also increased the ability of PMN to phagocytose heat-killed C. albicans organisms in a dose-dependent manner, without opsonization by antibodies or complement-derived products. In the same concentration range, IL-15 was as effective as gamma interferon (IFN-gamma ) and IL-2 in increasing the C. albicans growth-inhibitory activity of PMN. Taken together, these results suggest that IL-15 is a potent stimulant of both proinflammatory and antifungal activities of PMN, activating several antimicrobial functions of PMN involved in the cellular response against C. albicans.

* Corresponding author. Mailing address: Istituto di Microbiologia, Via Santena 9, 10126 Turin, Italy. Phone: 39 11 670.6609. Fax: 39 11 663.6436.

Infect Immun, June 1998, p. 2640-2647, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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